Biomedical subjects

Martha E Payne

Publications and source records attributed to Martha E Payne.

At least 19 recordsLinked to original sources

PubMed2006

Food group intake and brain lesions in late-life vascular depression.

BACKGROUND: Studies indicate that diet may be related to the occurrence of brain lesions. The cross-sectional association between food intake and brain lesion volumes in late-life depression was examined in a cohort of elderly individuals with current or prior depression. METHODS: Food intake was assessed in 54 elderly vascular depression subjects (vascular depression defined by presence of hyperintensities on brain MRI) using a Block 1998 food frequency questionnaire. Food and kilocalorie intake were determined. Brain lesion volumes were calculated from MRI. Subjects were aged 60 or over and were participants in a longitudinal study of major depression. All subjects received psychiatric assessment and treatment, and medical comorbidity assessments. RESULTS: High-fat dairy and whole grains were significantly positively correlated with brain lesion volume, while other food groups were not significantly associated with lesion volume. In multivariable analyses, controlling for age, sex, hypertension, diabetes and total kilocalories, the positive association with lesion volume remained significant for both high-fat dairy and whole grains. CONCLUSIONS: High fat dairy and whole grain consumption may be associated with brain lesions in elderly subjects with depression.

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PubMed2006

Aging, gender, and the elderly adult brain: an examination of analytical strategies.

We sought to examine the relations between age, gender and brain volumes in an elderly population; we also sought to examine ways of measuring these relations. Three sets of analyses were used: correlational analyses, in which correlations between independent variables and brain volumes were calculated without correction for intracranial volume (ICV); covariational analyses, in which ICV was used as a covariate in regression equations; and ratio analyses, in which the dependent variable was the ratio of brain volume to ICV. These analyses yielded similar results, except that (as expected) adjusting for ICV altered estimates of gender differences. Analyses of age showed decreases in left caudate, putamen, and right hippocampus and an increase in CSF, a result generally in accord with previous findings. However, we also found a significant decrease of white-matter volumes and no significant decrease in total gray-matter volumes. Correlational analyses showed that men did not always have larger volumes despite their larger head size; women generally had larger volumes after adjusting for ICV. We found no age-gender interactions.

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PubMed2006

Differences in brain volumes among males and female hormone-therapy users and nonusers.

Numerous studies have shown gender differences in the brain volumes of elderly adults. Some evidence shows that higher estrogen levels may be neuroprotective, suggesting that hormone therapy (HT) may in part be responsible for these gender differences; however, few studies have examined the relation between HT and brain volumes. Brain volumes of caudate, putamen, hippocampus, gray matter, white matter, white-matter lesions, and cerebrospinal fluid were measured on magnetic resonance imaging scans. A comprehensive neuropsychological battery was administered. Women were separated into two groups based on HT use, and we used multiple regression analyses to compare these groups with one another and with men. Results of brain-volume measurements showed that HT users had significantly less gray matter and more cerebrospinal fluid than nonusers. Results of the neuropsychological testing showed that HT users performed better on the Shipley Vocabulary Test than males did.

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PubMed2006

Predicting memory decline in normal elderly: genetics, MRI, and cognitive reserve.

Major predictors of Alzheimer's disease (AD) include apolipoprotein E (APOE)-epsilon4, hippocampal atrophy on magnetic resonance imaging (MRI), and memory dysfunction prior to diagnosis. We examined 159 normal elderly subjects with MRI and the California Verbal Learning Test (CVLT); 84 returned for longitudinal follow-up 5 years later. Analyses at baseline revealed significant variance in hippocampal volume accounted for by cerebral volume and age but not by APOE isoform. However, interactions involving APOE isoform and laterality were observed. As hypothesized, an APOE x time interaction was revealed for CVLT long-delay free recall: APOE-epsilon3/4 subjects had significantly poorer performance than APOE-epsilon3/3 subjects at follow-up. Forward stepwise multiple regression analysis predicting follow-up long-delay free recall selected baseline recall, followed by number of APOE-epsilon4 alleles, followed by left-hippocampal volume. Age and sex did not enter into the model. We conclude that APOE-epsilon4 predicts longitudinal memory decline in healthy controls and that MRI morphometry of hippocampus adds slightly to predictive value.

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PubMed2006

Dorsolateral prefrontal cortex and anterior cingulate cortex white matter alterations in late-life depression.

BACKGROUND: The dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) are critical for mood regulation. Alterations in the white matter connections of these regions may impair their role in mood regulation and increase the risk of developing depression. This study used diffusion tensor imaging to examine for white matter microstructural abnormalities of these regions and of central white matter structures in late-life depression. METHODS: One hundred six elderly depressed subjects and eighty-four elderly nondepressed subjects underwent clinical assessment and diffusion tensor imaging. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in regions of interest placed in the white matter of the DLPFC, ACC, corpus callosum, and internal capsule. Differences between groups were assessed, controlling for age, sex, and total cerebral volume. RESULTS: After controlling for covariates, depressed subjects had significantly lower FA values in white matter of the right ACC, bilateral superior frontal gyri, and left middle frontal gyrus. There were no significant differences in ADC values. CONCLUSIONS: Lower FA, representing lower tissue organization, is observed in depressed elders in the DLPFC and right ACC. These findings support the hypothesis that altered connectivity between brain regions contributes to the risk of depression.

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PubMed2006

White matter and subcortical gray matter lesion volume changes and late-life depression outcome: a 4-year magnetic resonance imaging study.

BACKGROUND: Cross-sectional studies have shown that late-onset depression is associated with larger deep white matter lesions (WMLs) and subcortical gray matter lesions (GMLs). In a longitudinal analysis, we examined changes in deep WMLs and subcortical GMLs in older depressed and nondepressed subjects over a 4-year period. METHODS: Brain magnetic resonance imaging (MRI) scans were obtained on 164 depressed and 126 healthy subjects aged 60 years or older at baseline, and 2 and 4 years after recruitment. WMLs and GMLs were measured using a semiautomated technique. We used repeated-measures analysis of covariance to determine cross-sectional lesion volume differences, whether lesion volume changes differed between patients and controls, and the effect of lesion volume changes on outcome in late-life depression. RESULTS: Mean volumes of lesions for the depressive group were 6.51, 8.18 and 7.75 cm2 for WMLs and 0.23, 0.30 and 0.34 cm2 for GMLs at baseline, 2-year and 4-year follow-up, respectively. Mean volumes of lesions for the control group were 4.83, 6.22 and 6.45 cm2 for WMLs and 0.17, 0.25 and 0.23 cm2 for GMLs at baseline, 2-year and 4-year follow-up, respectively. Cross-sectional between-group mean lesion volumes were significantly different for each measure. However, the pattern of WML and GML volume changes over time was not significantly different between groups. Treatment outcome was associated with changes in total and white matter lesion volume over time. CONCLUSIONS: Lesion volume progression is associated with aging and the pathological condition of late-life depression. The mechanisms that produce these progressive lesion changes remain unclear. Treatments aimed at arresting lesion progression may play a role in the management of late-life depression.

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PubMed2006

White matter lesion volumes and caudate volumes in late-life depression.

BACKGROUND: Decreased caudate volumes and increased white matter lesions (WMLs) are associated both with aging and late-life depression, but the relationship between the two is unclear. We examined the association between WML and caudate volume, hypothesizing there would be a negative association, which would be stronger for WMLs located in anterior regions. We additionally hypothesized that this association would be stronger in depressed subjects. METHOD: This MRI study included 182 elderly depressed and 64 elderly control subjects. Our imaging analysis procedures divided the brain into anterior and posterior halves. WML volume in each half was calculated, as were left and right caudate volumes. A statistical model incorporating WML volumes, age, total brain volume, diagnosis, and gender was used to examine caudate volumes. RESULTS: WML volume was negatively associated with total and right caudate volume. This association was stronger for WMLs in the anterior half of the brain. Anterior WML volume was additionally negatively associated with right caudate volume in depressed subjects, but not in controls. CONCLUSIONS: Using unadjusted levels of significance, WML volume is negatively associated with right caudate volume in both older populations, but with left caudate volume only in depressed individuals. When statistical corrections for multiple comparisons are used, the finding is limited to a negative association between WML volume and right caudate volume, primarily in depressed subjects. This study demonstrates one mechanism by which WMLs may disrupt frontostriatal circuits.

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PubMed2006

Vascular nutritional correlates of late-life depression.

OBJECTIVE: The authors sought to examine the association of vascular nutritional factors and depression in an elderly cohort of depression (currently and recently depressed) and comparison (never depressed) subjects. METHOD: Nutrient intake over the past year was assessed in 196 elderly depression and comparison individuals with a Block 1998 food-frequency questionnaire. Nutrient intake, body mass index, and Keys score (a measure of the serum cholesterol-raising capacity of the diet) were determined. Subjects were age 60 and over and were participants in a longitudinal study of major depression. All subjects received psychiatric and medical comorbidity assessments; depression subjects also received psychiatric treatment. RESULTS: Vascular nutritional factors differed between depression and comparison subjects. The depression group had higher intake of saturated fat and cholesterol, higher body mass indices, lower alcohol intake, and higher Keys score than the comparison group. After controlling for age, sex, education, race, and medical comorbidity, associations remained for cholesterol, alcohol, and Keys score. Depression was found to be associated with overall dietary pattern as defined by total kilocalories, saturated fat, cholesterol, body mass index, polyunsaturated fat, sodium, and alcohol. CONCLUSIONS: This study provides evidence that dietary vascular risk factors differ in individuals with current or prior depression when compared with individuals with no history of depression.

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PubMed2005

Lobar distribution of lesion volumes in late-life depression: the Biomedical Informatics Research Network (BIRN).

White matter hyperintense lesions on T2-weighted images are associated with late-life depression. Little work has been carried out examining differences in lesion location between elderly individuals with and without depression. In contrast to previous studies examining total brain white matter lesion volume, this study examined lobar differences in white matter lesion volumes derived from brain magnetic resonance imaging. This study examined 49 subjects with a DSM-IV diagnosis of major depression and 50 comparison subjects without depression. All participants were age 60 years or older. White matter lesion volumes were measured in each hemisphere using a semiautomated segmentation process and localized to lobar regions using a lobar atlas created for this sample using the imaging tools provided by the Biomedical Informatics Research Network (BIRN). The lobar lesion volumes were compared against depression status. After controlling for age and hypertension, subjects with depression exhibited significantly greater total white matter lesion volume in both hemispheres and in both frontal lobes than did control subjects. Although a similar trend was observed in the parietal lobes, the difference did not reach a level of statistical significance. Models of the temporal and occipital lobes were not statistically significant. Older individuals with depression have greater white matter disease than healthy controls, predominantly in the frontal lobes. These changes are thought to disrupt neural circuits involved in mood regulation, thus increasing the risk of developing depression.

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PubMed2005

Greater MRI lesion volumes in elderly depressed subjects than in control subjects.

Hyperintense lesions in both white matter and gray matter on T2-weighted magnetic resonance imaging (MRI) are associated with late-life depression. This large study examined differences in gray and white matter lesion volumes on brain MRI between 253 elderly depressed and 146 control subjects. White matter and gray matter lesion volumes were measured in each hemisphere using a semi-automated segmentation process and compared against depression status. Depressed subjects exhibited significantly greater total white matter (mean 7.22 ml) and gray matter (mean 0.30 ml) lesion volumes in both hemispheres than did control subjects (mean 4.87 ml in white matter and 0.18 ml in gray matter). This difference remained statistically significant even after controlling for confounders such as age, sex, race and reports of hypertension, diabetes and heart disease. Patients with late-life depression have larger white matter lesion and gray matter lesion volumes than do control subjects. Future research should combine similar volumetric techniques with methods of identifying the location of lesions specific to late-life depression.

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PubMed2005

Brain morphometry, T2-weighted hyperintensities, and IQ in children with neurofibromatosis type 1.

BACKGROUND: Larger gray matter (GM) volume in healthy children is correlated with higher IQ. Children with neurofibromatosis type 1 (NF1) have larger brains, their magnetic resonance images frequently show T2-weighted hyperintensities, and their IQs are lower. OBJECTIVES: To confirm the hypotheses that (1) children with NF1 have larger GM and white matter volumes, (2) the greatest volume differences are in the frontal and parietal regions and in children with NF1 with hyperintensities, and (3) GM volume is inversely related to IQ in children with NF1. DESIGN: Wechsler Intelligence Scale for Children-Third Edition IQ testing and measurement of cerebral volumes and hyperintensities in brain magnetic resonance images were performed on 36 children with NF1 and on 36 matched relatives who served as control subjects. RESULTS: Gray matter and white matter volumes were significantly larger in children with NF1. The greatest difference was observed in cerebral white matter volume, predominantly in the frontal lobes, whereas the greatest difference in GM volume was in the temporal, parietal, and occipital regions. In controls, IQ was significantly related to GM volume, but in children with NF1, IQ was not inversely associated with GM volume, although IQs of children with NF1 were significantly lower. CONCLUSIONS: Children with NF1 do not have the normal relationship between GM volume and IQ. Larger GM volume in the posterior brain regions and larger white matter volumes in the frontal brain regions contribute to the larger brain volume in children with NF1.

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PubMed2005

Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression.

CONTEXT: Polymorphisms in the promoter region of the serotonin transporter gene (5-HTTLPR) influence transcription and may play a role in the pathogenesis and course of depression. Recent research demonstrates that specific polymorphisms may be associated with differences in hippocampal volumes in subjects with depression. OBJECTIVE: To examine associations between 5-HTTLPR genotype and hippocampal volumes in elderly control subjects and elderly subjects classified as having early or late onset of depression. DESIGN: Cohort study examining baseline characteristics. PARTICIPANTS: Subjects were community dwelling and 60 years or older. Using a definition of early-onset depression as depression first occurring at 50 years or younger, we examined 72 subjects with early-onset depression, 63 subjects with late-onset depression, and 83 healthy control subjects. MAIN OUTCOME MEASURES: All subjects underwent genotyping for the 5-HTTLPR and underwent brain magnetic resonance imaging. Analyses of hippocampal volumes were controlled for total cerebral volume, age, and sex. RESULTS: The interaction between diagnosis and 5-HTTLPR genotype was statistically significant for the right hippocampus (P = .04). Subjects with late-onset depression who were homozygous for the long (L) allele (L /L genotype) had significantly smaller right hippocampal volumes than did L /L subjects with early-onset depression (P = .046) or L /L control subjects (P = .01). Post hoc analyses showed that later age of depression onset was associated with smaller hippocampal volumes in subjects with the L /L genotype, but earlier age of onset was associated with smaller hippocampal volumes in subjects who were homozygous for the short (S) allele (S/S genotype). CONCLUSIONS: Subjects with late-onset depression who were homozygous for the L allele exhibited smaller hippocampal volumes than other groups. Genotype also mediated the effect of age of onset on hippocampal volumes. Our findings differ from previous work; however, we examined an older and larger cohort of subjects than previous studies. Possible explanations for these findings include interactions between the serotonergic system and neurotrophic factors or cortisol response to stresses, each of which may affect hippocampal volumes.

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PubMed2005

Biological and social predictors of long-term geriatric depression outcome.

OBJECTIVE: In this study, we examined 204 older depressed individuals for up to 64 months to determine factors related to depression outcome. We hypothesized that both presence of vascular brain lesions seen on baseline magnetic resonance imaging (MRI) scans and lower baseline social support measures would be related to worse depression outcome. METHOD: At study entry, all subjects were at least 59 years old, had a diagnosis of major depression, and were free of other major psychiatric illness and primary neurological illness, including dementia and stroke. Depression was diagnosed via structured interview and clinical assessment by a geriatric psychiatrist who completed a Montgomery Asberg Depression Rating Scale (MADRS) to determine severity of depression. Subjects provided self-report data on social support variables and ability to perform basic and instrumental activities of daily living (ADL, IADL). All subjects agreed to have a baseline standardized MRI brain scan. Ratings of severity of hyperintensities were determined for the periventricular white matter, deep white matter, and subcortical gray matter by two readers who decided by consensus. Treatment was provided by geropsychiatrists following clinical guidelines. Using mixed models to analyze the data, we determined the effect of a variety of demographic, social and imaging variables on the trajectory of MADRS score, the outcome variable of interest. RESULTS: MADRS scores decreased steadily over time. In a final HLM model, in which time since entry, a baseline time indicator, age, gender, education and Mini-mental State Examination score were controlled, subjective social support, instrumental ADL impairment, subcortical gray matter severity, and the interactions of time with social network and with subcortical gray matter lesions remained significantly associated with MADRS score. CONCLUSIONS: Both social and biological factors at baseline are associated with longitudinal depression severity in geriatric depression.

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PubMed2005

Cortical white matter microstructural abnormalities in bipolar disorder.

This article reports on preliminary findings describing microstructural abnormalities in the white matter of cortical areas thought to be associated with bipolar disorder. In all, 14 patients with bipolar disorder and 21 nonpsychiatrically ill control subjects underwent MR imaging including a diffusion tensor imaging (DTI) pulse sequence (six directions, b=1000 mm(2)/s). DTI data were analyzed on a workstation using a program that allowed calculation of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) within the following three white matter fiber tracts bilaterally: the orbital frontal cortex, and the superior and middle frontal gyri. These values were compared across patient groups. The left and right orbital frontal white matter exhibited significantly higher ADC values in bipolar subjects than control subjects on both the left (p=0.028) and right (p=0.011). Microstructural changes in the white matter of the orbital frontal areas as reflected by increased ADC values appear to be associated with bipolar disorder. Further research is needed to better understand the interaction of microstructural changes and bipolar symptoms and whether these changes are specific to bipolar disorder.

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PubMed2004

Clinical characteristics of magnetic resonance imaging-defined subcortical ischemic depression.

BACKGROUND: There is a substantial body of research supporting the vascular depression hypothesis of late-life depression. To update this hypothesis so it incorporates recent research, we propose that the term subcortical ischemic vascular depression may be a more accurate representation of the disease process. We sought to investigate this diagnosis as a construct by examining differences between depressed subjects with and without magnetic resonance imaging defined subcortical ischemic vascular depression. METHODS: This case-control study examined 139 depressed elderly subjects. Demographic data, psychiatric, medical, and family history, depressive symptomatology, and functional impairment were compared between groups dichotomized based on neuroimaging findings. RESULTS: Seventy-five (54%) of the subjects met neuroimaging criteria for subcortical ischemic vascular depression. Age was most strongly associated with increased prevalence of subcortical ischemic vascular depression. Lassitude and a history of hypertension were also positively associated with the diagnosis; a family history of mental illness and loss of libido were negatively associated with the diagnosis. CONCLUSIONS: These data support that subcortical ischemic vascular depression may be a specific syndrome from other types of late-life depression. Further research is needed to further characterize this disorder, particularly in regards to cognitive function and treatment implications.

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PubMed2004

Late-life depression and microstructural abnormalities in dorsolateral prefrontal cortex white matter.

OBJECTIVE: The purpose of this study was to determine whether microstructural abnormalities in the white matter of the dorsolateral prefrontal cortex are associated with late-life depression. METHOD: Seventeen elderly depressed subjects were compared with 16 elderly subjects who were not depressed. Diffusion tensor imaging was used to measure the fractional anisotropy of the white matter in the dorsolateral prefrontal cortex's superior and middle frontal gyri bilaterally and in the left occipital lobe as a control region. The authors compared results between groups while controlling for age, sex, and comorbid medical disorders. RESULTS: Even after controlling for age, sex, hypertension, and heart disease, the authors found significantly lower fractional anisotropy values in the right superior frontal gyrus white matter of depressed patients than comparison subjects. CONCLUSIONS: Microstructural changes in the white matter of the right superior frontal gyrus are associated with late-life depression. Further work is needed to determine how these changes contribute to depression outcomes.

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PubMed2003

Apolipoprotein E genotype and subcortical vascular lesions in older depressed patients and control subjects.

BACKGROUND: Several studies have linked geriatric depression with cerebrovascular disease. The apolipoprotein E gene (APOE) epsilon 4 allele has been associated with a variety of late-life neuropsychiatric disorders, including Alzheimer's disease, vascular dementia, and depression. METHODS: The sample consisted of 145 elderly depressive individuals and 100 nondepressed elderly control subjects. After a standardized clinical assessment, all subjects underwent a magnetic resonance imaging brain scan. Volumes of subcortical white and gray matter lesions were determined using a semi-automated method. Apolipoprotein E genotype was determined on blood sample using a standard protocol. A series of linear regression models were developed to assess the relationships between APOE genotype and white and gray matter lesion volumes. RESULTS: Older age, lower Mini-Mental State Examination score, and having any APOE epsilon 4 allele were each correlated with gray-matter lesion volume in depressed patients. Apolipoprotein E genotype was not associated with any lesion volume among control subjects. In a subsequent linear regression model, gray matter lesion volume was associated with older age, having at least one APOE epsilon 4 allele, and white matter lesion volume among depressed patients. CONCLUSIONS: These results are consistent with previous reports linking cerebrovascular disease and APOE genotype. Further studies are needed to replicate this finding in elderly depressive individuals and to explain the relationship between the APOE locus and development of central nervous system vascular pathology.

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PubMed2003

Subcortical lesion severity and orbitofrontal cortex volume in geriatric depression.

Previous studies have shown a reduction of orbital frontal cortex volume and an increase in magnetic resonance imaging signal hyperintensities in geriatric depression. We aimed to assess the relationship between subcortical gray- and deep white-matter lesions and orbital frontal cortex volume in elderly depressives and controls. The study included 41 elderly depressed patients and 41 age-matched control subjects. The orbital frontal cortex volume was measured in both hemispheres using a standardized MRI procedure. Signal hyperintensities were rated on (T2)-weighted MRI with qualitative lesion analyses performed according to an established hyperintensity classification system. After controlling for total cerebral hemisphere, age and sex, the geriatric depressed subjects had significant reduction in orbital frontal cortex volume and compared with the control group. Multiple linear regression modeling indicated that reduced orbital frontal cortex volumes were significantly associated with increased subcortical gray-matter lesions. Our study confirmed the reduction of OFC volume in geriatric depressed subjects. We also suggest that subcortical lesions may decrease OFC volume. Further studies are needed to understand how subcortical lesions may be related to OFC volume changes.

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