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G S Zubenko

Publications and source records attributed to G S Zubenko.

At least 19 recordsLinked to original sources
PubMed1999

Prospective study of risk factors for Alzheimer's disease: results at 7.5 years.

OBJECTIVE: The primary goal of this study was to evaluate increased platelet membrane fluidity as a putative risk factor for Alzheimer's disease and its relationship to the APOE epsilon4 genotype. METHOD: This report describes the results of a prospective, longitudinal study of 330 initially asymptomatic, first-degree relatives of probands with Alzheimer's disease. RESULTS: Nine incident cases of Alzheimer's disease were detected during the first 2,220 subject-years of the follow-up period. Age, increased platelet membrane fluidity, and the APOE epsilon4 allele made significant independent contributions to the risk of developing Alzheimer's disease, while sex and years of education did not. Increased platelet membrane fluidity was associated with incident Alzheimer's disease cases between the ages of 64 and 71, while the epsilon4 allele was associated with incident Alzheimer's disease cases from age 64 until at least age 80. CONCLUSIONS: These results indicate that increased platelet membrane fluidity is not produced by the APOE epsilon4 allele. Instead, increased platelet membrane fluidity and the epsilon4 allele appear to make significant independent contributions to the risk of developing Alzheimer's disease among the first-degree relatives of patients with this disorder. Moreover, the age ranges over which these risk factors operate appear to be different.

Adult↗
PubMed1998

Linkage and association analysis of chromosomal regions containing genes related to neuroendocrine or serotonin function in families with early-onset, recurrent major depression.

Recurrent unipolar depression with an early age of onset is a severe form of unipolar depression that has both genetic and environmental components. We genotyped the members of 16 families identified by probands with early onset (< or = 25 years), recurrent unipolar, major depression for 38 simple sequence tandem repeat polymorphisms (SSTRPs) from chromosomal regions containing 12 genes involved in neuroendocrine or serotonergic functioning. Pairwise linkage analysis was performed with the software package FASTLINK. The affected phenotype was defined four ways, and both dominant and recessive models of depression were analyzed. Seven SSTRPs showed lod scores > 1.00 at theta values between 0.10-0.20. The members of an additional 18 families were genotyped for these seven SSTRPs, and the complete sample of 34 families was evaluated using lod score analysis, affected pedigree member linkage analysis, and within-family association analysis. Evidence for linkage between D11S929 and affective illness remained positive, necessitating the analysis of four additional SSTRPs within 3 cM of D11S929. After all confirmatory analyses were completed, no evidence suggestive of linkage remained between any of the 38 SSTRPs and the affected phenotypes.

Depressive Disorder↗
PubMed1998

A genome survey for novel Alzheimer disease risk loci: results at 10-cM resolution.

We completed a systematic survey of the human genome, conducted at an average resolution of 10 cM, for the identification of simple sequence tandem repeat polymorphisms (SSTRPs) that target new risk genes for Alzheimer disease (AD) by virtue of linkage disequilibrium. The efficiency of our association study was enhanced by genotyping pools of DNA from autopsy-confirmed cases with AD and matched controls. Allelic associations with AD were observed for 6 of the 391 SSTRPs in the CHLC Human Screening Set/Weber Version 6 (Research Genetics, Inc., Huntsville, AL): D1S518, D1S547, D10S1423, D12S1045, D19S178, and DXS1047. These allelic associations were replicated in an independent sample of autopsied AD cases and controls recruited from a geographically disparate site. The association of the large D19S178 alleles with AD appeared to arise from linkage disequilibrium with the APOE epsilon 4 allele, whose effect on increasing the risk of AD has been established. None of the remaining SSTRPs was in close proximity to loci previously reported to influence the risk of developing AD. Instead, they may identify five novel AD susceptibility loci.

Age of Onset↗
PubMed1998

Initial results of a genome survey for novel Alzheimer's disease risk genes: association with a locus on the X chromosome.

As the initial step in a systematic genome survey, 16 simple sequence tandem repeat polymorphisms that span the X chromosome at an average spacing of 10 cM were examined for allelic associations with typical-onset Alzheimer's disease (AD). The efficiency of this survey was substantially enhanced by genotyping pools of genomic DNA from 50 autopsy-confirmed AD cases and 50 autopsied controls who were similar in sex ratio, race, and age at death. The frequency of the DXS1047 202-bp allele was twice as common among AD cases (0.45 +/- S.E. 0.06) than controls (0.22 +/- S.E. 0.05), a finding that was reproduced in an independent and geographically disparate sample. Consistent with Hardy-Weinberg equilibrium, the proportion of women with AD who carried the 202-bp allele, 73% was nearly double that observed for men with AD, 38%. However, the frequency of the 202-bp allele was similar for men and women and the presence of this allele did not affect the age at onset of dementia in either sex. Furthermore, the frequency of the DXS1047 202-bp allele in AD cases and controls was unaffected by the APOE genotype, indicating that these two loci modulate AD risk independently. Finally, the frequency of the 202-bp allele among 50 autopsy-confirmed cases of Parkinson's disease (0.29 +/- S.E. 0.06) was indistinguishable from the control value, reflecting relative specificity for this allelic association with AD.

Adult↗
PubMed1998

Initial results of a genome survey for novel Alzheimer's disease risk genes: association with a locus on the X chromosome.

As the initial step in a systematic genome survey, 16 simple sequence tandem repeat polymorphisms that span the X chromosome at an average spacing of 10 cM were examined for allelic associations with typical-onset Alzheimer's disease (AD). The efficiency of this survey was substantially enhanced by genotyping pools of genomic DNA from 50 autopsy-confirmed AD cases and 50 autopsied controls who were similar in sex ratio, race, and age at death. The frequency of the DXS1047 202-bp allele was twice as common among AD cases (0.45+/-S.E. 0.06) than controls (0.22+/-S.E. 0.05), a finding that was reproduced in an independent and geographically disparate sample. Consistent with Hardy-Weinberg equilibrium, the proportion of women with AD who carried the 202-bp allele, 73% was nearly double that observed for men with AD, 38%. However, the frequency of the 202-bp allele was similar for men and women and the presence of this allele did not affect the age at onset of dementia in either sex. Furthermore, the frequency of the DXS1047 202-bp allele in AD cases and controls was unaffected by the APOE genotype, indicating that these two loci modulate AD risk independently. Finally, the frequency of the 202-bp allele among 50 autopsy-confirmed cases of Parkinson's disease (0.29+/-S.E. 0.06) was indistinguishable from the control value, reflecting relative specificity for this allelic association with AD.

Adult↗
PubMed1998

Morbidity of homebound versus inpatient elderly psychiatric patients.

This study compares the demographic and clinical characteristics of homebound (HB) elders referred for psychiatric services (N = 251) with those of inpatients (IP) admitted to a geriatric psychiatry unit (N = 594). Demographically, HB patients were older (78.8 vs 74.7 years), were more likely to be women (83% vs 68%), were widowed (54% vs. 44%), and had fewer years of education (10.3 vs. 11.1), but were similar in race, income, and proportion living alone. Clinically, HB patients had less functional disability, less severe depression, less cognitive impairment, and fewer medical problems. However, they were similar in the distribution of most psychiatric diagnoses except dementia (higher in the IP group) and dementia with depression (higher in the HB group). Outcome data for the HB group over 15 (range, 1 to 38) months revealed medical hospitalization in 20.7%, psychiatric hospitalization in 16.3%, nursing home placement in 9.2% and mortality in 8.4%. These preliminary data show that the HB group had psychiatric problems that were comparable to those of the IP group but were not as severely impaired.

Age Distribution↗
PubMed1998

Determinants of spontaneous extrapyramidal symptoms in elderly psychiatric inpatients diagnosed with Alzheimer's disease, major depressive disorder, or psychotic disorders.

Extrapyramidal symptoms (EPS) occur more frequently in dementia of the Alzheimer's type (DAT) than in normal aging. Other late-life mental disorders, however, have also been associated with EPS. To examine whether EPS are increased in DAT patients relative to neuropsychiatric control subjects, the authors compared EPS in 127 neuroleptic-free elderly patients diagnosed with either DAT, major depressive disorder (MDD), or a psychotic disorder (SCHIZ/DELUS). They also examined whether depressive or psychotic symptoms were associated with EPS independently of diagnosis. Severity of parkinsonian rigidity was found to be independently associated with DAT. Rank order of rigidity was DAT > MDD > SCHIZ/DELUS. Bradykinesia, although not associated with diagnostic group, was positively correlated with withdrawn depression. These findings suggest that rigidity is associated with DAT independently of any concurrent psychotic or depressive process, whereas bradykinesia does not appear to be specific to DAT among late-life neuropsychiatric illnesses.

Age Factors↗
PubMed1998

Is delirium different when it occurs in dementia? A study using the delirium rating scale.

The authors studied 61 geropsychiatric patients with delirium from a cohort of 843 consecutive admissions to a geriatric clinical research unit. A central study goal was to assess how the presence of dementia affected the presentation of delirium. Eighteen delirious (D) and 43 delirious-demented (D-D) patients were compared on the Delirium Rating Scale (DRS), Mini-Mental State Examination (MMSE), Brief Psychiatric Rating Scale (BPRS), and EEG. D-D patients had lower MMSE scores, but no differences were found in total DRS or BPRS scores or in EEG grade. DRS items were similar in the two groups except that D-D had more cognitive impairment than D. An exploratory principal components analysis of DRS items identified two core factors. The authors conclude that the presentation of delirium in the setting of concurrent dementia is very similar to delirium without dementia, with subtle differences probably attributable to dementia.

Aged↗
PubMed1997

Medical comorbidity in elderly psychiatric inpatients.

A multidisciplinary diagnostic evaluation was performed for 868 older psychiatric inpatients during a 46-month interval. A total of 402 (46%) met DSM-III-R criteria for organic mental disorders, 329 (38%) had mood disorders, 90 (10%) had psychotic disorders, and 47 (5%) had other mental disorders or conditions. Concurrent medical problems were systematically assessed and classified according to ICD-9-CM criteria. The patients suffered from a mean of 5.6 +/- 3.1 (SD) active medical problems (range 0-18). This level of medical comorbidity was significantly greater than that of older psychiatric outpatients and comparable to that of elderly inpatients in general medical hospitals. When the effects of age and education were controlled for, there were no significant differences in mean numbers of medical problems among the four groups of psychiatric inpatients. An association of major depression with diseases of the digestive system was observed and may be related to peripheral autonomic dysregulation.

Aged↗
PubMed1997

Genetic segregation analysis of early-onset recurrent unipolar depression.

Major depression is a relatively common psychiatric disorder that can be quite debilitating. Family, twin, and adoption studies indicate that unipolar depression has both genetic and environmental components. Early age at onset and recurrent episodes in the proband each increase the familiarity of the illness. To investigate the potential genetic underpinnings of the disease, we have performed a complex segregation analysis on 832 individuals from 50 multigenerational families ascertained through a proband with early-onset recurrent unipolar major depression. The analysis was conducted by use of regressive models, to test a variety of hypotheses to explain the familial aggregation of recurrent unipolar depression. Analyses were conducted under two alternative definitions of affection status for the relatives of probands: (1) "narrow," in which relatives were assumed to be affected only if they were diagnosed with recurrent unipolar depression; and (2) "broad," in which relatives were assumed to be affected if diagnosed with any major affective illness. Under the narrow-definition assumption, the model that best explains these family data is a transmitted (although non-Mendelian) recessive major effect with significant residual parental effects on affection status. Under the broad-definition assumption, the best-fitting model is a Mendelian codominant major locus with significant residual parental and spousal effects.

Adolescent↗
PubMed1997

Mortality of elderly patients with psychiatric disorders.

OBJECTIVE: The goal of this study was to evaluate the impact of common late-life mental disorders on the life expectancy and causes of death of older psychiatric patients. METHOD: The study population consisted of 809 older psychiatric patients who met DSM-III-R criteria for organic mental disorders, mood disorders, or psychotic disorders and who were discharged after a comprehensive multidisciplinary evaluation and acute inpatient treatment for their behavioral disorders. Dates and causes of death during a 5.75-year follow-up period were provided by the Pennsylvania Department of Health. Univariate and multivariate survival procedures were used to compare the survival rates of the three groups to each other and to a reference population of Pennsylvania residents. Causes of death were also tabulated according to ICD-9-CM and compared across the groups. RESULTS: Age, gender, race, and medical comorbidity made significant independent contributions to survival. When these variables were controlled, the survival of patients with organic mental disorders was less than half of that for patients with mood or psychotic disorders. However, all three groups experienced higher rates of mortality than the reference population, with standardized mortality ratios of 1.5 to 2.5. Deaths occurred from the usual spectrum of natural causes, with the exception that patients with mood disorders were more likely to have died from disorders of the digestive system and suicide. CONCLUSIONS: The mental disorders of late life have a significant negative impact on the survival of older psychiatric patients.

Age Factors↗
PubMed1996

Association of the APOE epsilon 4 allele with clinical subtypes of late life depression.

The APOE genotypes of 45 elderly inpatients with major depression were determined to investigate the relationship of this disorder to irreversible dementia in late life. We specifically tested the hypothesis that the frequency of the APOE epsilon 4 allele is elevated in depressed elders with cognitive impairment or psychotic features, subtypes that have been reported to be at increased risk of developing Alzheimer's disease (AD). The frequency of epsilon 4 allele was not elevated in the overall group of 45 inpatients and, contrary to our expectation, was not associated with cognitive impairment in this group. In contrast, the epsilon 4 allele frequency for the patients with psychotic features was nearly four times that for the patients without psychotic features and nearly double that of elderly controls. These data suggest that elderly depressed inpatients with cognitive impairment are at risk for developing AD by an epsilon 4-independent pathway, while those with psychotic features are at risk for developing AD by an epsilon 4-dependent pathway. These findings suggest that subtypes of idiopathic major depression in late life may serve as landmarks that distinguish separable pathogenetic pathways to AD.

Age of Onset↗
PubMed1996

MRI changes in schizophrenia in late life: a preliminary controlled study.

The aim of this pilot study was to compare cerebral changes on magnetic resonance imaging (MRI) scans in elderly schizophrenic subjects with those in psychiatric and normal control subjects. We compared the MRIs of 19 subjects with schizophrenia, 19 age- and gender-matched subjects with recurrent major depression, and 19 age- and gender-matched nonpsychiatric control subjects. Deep white matter hyperintensities (DWMH) in right posterior regions were significantly more prominent in the schizophrenic group than in the two comparison groups. Total ratings of MRI abnormalities were significantly related to age in both the normal control and schizophrenic groups, but not in the depressive group. Age of onset was positively associated with total ratings in the depressive group, but not in the schizophrenic group. Thus, a subset of elderly patients with schizophrenia appear to have cerebral white matter abnormalities; such abnormalities may not be confined to late-onset schizophrenia. Systematic MRI studies of early- and late-onset schizophrenia in late life are needed to resolve this question.

Adolescent↗
PubMed1996

Prospective study of increased platelet membrane fluidity as a risk factor for Alzheimer's disease: results at 5 years.

OBJECTIVE: The primary goal of this study was to evaluate increased platelet membrane fluidity as a putative risk factor for Alzheimer's disease. METHOD: This report describes the initial results of a prospective, longitudinal study of 330 initially asymptomatic, first-degree relatives of probands with Alzheimer's disease. RESULTS: Five incident cases of Alzheimer's disease were detected during the first 1,582 subject-years of the follow-up period. The age-specific incidence of Alzheimer's disease was several-fold higher than corresponding figures that were obtained in two prospective community studies. Most important, both age and increased platelet membrane fluidity made significant independent contributions to the risk of developing Alzheimer's disease. CONCLUSIONS: These results validate age and a family history of Alzheimer's disease as risk factors for this disorder and provide the first prospective evidence of increased platelet membrane fluidity as a biological risk factor for Alzheimer's disease.

Adult↗
PubMed1995

Duration of neuroleptic treatment and prevalence of tardive dyskinesia in late life.

BACKGROUND: Although increasing age is the most consistently cited risk factor for the development of tardive dyskinesia for patients in the second to sixth decades of life, this relationship may not hold within geriatric populations. METHODS: Consecutively admitted geropsychiatric inpatients were examined with the Abnormal Involuntary Movement Scale within 72 hours of admission; comprehensive demographic, diagnostic, and psychometric data were also obtained. RESULTS: Seventy-four (19.2%) of 386 patients received diagnoses of dyskinesia. Lifetime duration of neuroleptic use was strongly correlated with dyskinesia rates. After accounting for the effect of lifetime duration of neuroleptic use in a stepwise logistic regression, only associations with Global Assessment Scale score and presence of dental problems remained statistically significant. In comparison with the duration of neuroleptic use, however, the contribution of these factors was minor. Sixteen percent of patients with less than 3 months of neuroleptic use, 29% with 3 to 12 months of neuroleptic use, 30% with 1 to 10 years of neuroleptic use, and 41% with more than 10 years of neuroleptic use had dyskinesia. Compared with patients with no history of neuroleptic treatment, the relative risks for these durations of neuroleptic use were 1.62 (95% confidence limits [CL], 0.81, 3.24), 2.89 (95% CL, 1.50, 5.55), 3.08 (95% CL, 1.66, 5.70), and 4.11 (95% CL, 2.12, 7.96), respectively. CONCLUSIONS: Within elderly populations, duration of exposure to neuroleptics is the strongest predictor of risk for tardive dyskinesia, and this risk increases rapidly within the first year of total lifetime neuroleptic use.

Age Factors↗
PubMed1995

Complicated grief and bereavement-related depression as distinct disorders: preliminary empirical validation in elderly bereaved spouses.

OBJECTIVE: This study sought to determine whether a set of symptoms interpreted as complicated grief could be identified and distinguished from bereavement-related depression and whether the presence of complicated grief would predict enduring functional impairments. METHOD: Data were derived from a study group of 82 recently widowed elderly individuals recruited for an investigation of physiological changes in bereaved persons. Baseline data were collected 3-6 months after the deaths of the subjects' spouses, and follow-up data were collected from 56 of the subjects 18 months after the baseline assessments. Candidate items for assessing complicated grief came from a variety of scales used to evaluate emotional functioning (e.g., the Hamilton Depression Rating Scale, the Brief Symptom Inventory). The outcome variables measured were global functioning, medical illness burden, sleep, mood, self-esteem, and anxiety. RESULTS: A principal-components analysis conducted on intake data (N = 82) revealed a complicated grief factor and a bereavement-depression factor. Seven symptoms constituted complicated grief: searching, yearning, preoccupation with thoughts of the deceased, crying, disbelief regarding the death, feeling stunned by the death, and lack of acceptance of the death. Baseline complicated grief scores were significantly associated with impairments in global functioning, mood, sleep, and self-esteem in the 56 subjects available for follow-up. CONCLUSIONS: The symptoms of complicated grief may be distinct from depressive symptoms and appear to be associated with enduring functional impairments. The symptoms of complicated grief, therefore, appear to define a unique disorder deserving of specialized treatment.

Age Factors↗