Biomedical subjects

Douglas R McQuoid

Publications and source records attributed to Douglas R McQuoid.

At least 19 recordsLinked to original sources

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.

Age of Onset↗

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

Residual symptoms in older patients treated for major depression.

OBJECTIVE: The purpose of this study was to identify residual symptoms in a sample of older adults treated for major depression and compare individual symptoms present at baseline with those at three months by remission status. METHODS: The sample was comprised of 229 patients with DSM-IV major depression who were participants in the NIMH Mental Health Clinical Research Center at Duke University. Symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: At three months, 86 patients (37.6%) had remitted, or had a MADRS score less than or equal to 9. In the remitted group, the most frequently reported symptoms at three months were inner tension and lassitude. Among nonremitters, the most frequently reported symptoms were reported and apparent sadness, as well as lassitude and inner tension. In the sample as a whole, the symptoms most likely to be present at baseline but not three months were pessimistic and suicidal thoughts, while the most frequently reported emergent symptoms were reduced appetite and inner tension. Patients were much more likely to no longer have a particular symptom than to acquire a new symptom. Overall, the symptoms present at three months were not severe in either group. CONCLUSIONS: In older adults treated for major depression, residual symptoms at three months may include emergent symptoms as well as persistent symptoms, and are likely to include symptoms of anxiety as well as sadness. These findings have clinical implications for the treatment of late-life depression.

Affect↗

PubMed2005

Impact of symptoms of generalized anxiety disorder on the course of late-life depression.

OBJECTIVE: The authors sought to examine the effect of symptoms of generalized anxiety disorder (GAD) on acute course of depression in a group of older depressed patients. METHODS: Authors assessed GAD symptoms in a sample of 204 patients age 60 and older with unipolar major depression. Patients were treated naturalistically by study geriatric psychiatrists using a treatment guideline for geriatric depression and assessed with the Montgomery-Asberg Depression Rating Scale. They were dichotomized as meeting or not meeting GAD symptom criteria. The groups were analyzed by Cox proportional-hazards models. RESULTS: There were 138 remitters and 66 non-remitters. After analysis controlled for benzodiazepine use, stressful life events, social support, and functional status, having GAD symptoms was associated with longer time-to-remission. CONCLUSIONS: Older depressed patients with GAD have a worse outcome than those without anxiety. Future studies will need to determine the appropriate role of benzodiazepines and other anxiolytics in the treatment of older depressed patients with symptoms of GAD.

Acute Disease↗

PubMed2005

Hippocampal volume as a predictor of short-term ECT outcomes in older patients with depression.

OBJECTIVE: The authors examined the relationship between hippocampal volume and acute electroconvulsive therapy (ECT) outcomes. METHODS: Depression was measured by Montgomery-Asberg Depression Rating Scale (MADRS) scores, and hippocampal volume was assessed by magnetic resonance imaging. RESULTS: After controlling for baseline MADRS score, larger right-hippocampal volume was associated with higher MADRS scores after an index course of ECT. CONCLUSION: These results are the converse of those obtained in a study assessing the relationship between hippocampal volume and pharmacotherapy. The findings suggest a need for further study in this area.

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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.

Age Factors↗

PubMed2004

Medical comorbidity in late-life depression.

OBJECTIVES: Medical comorbidity is common in elderly patients with depression, however the difference between depressed and non-depressed elderly populations is not well established. Additionally, differences between subgroups of depressed populations, including those with MRI-defined vascular depression and those with late-onset compared with early-onset depression are not well described. METHODS: We compared self-report of medical disorders between 370 depressed elders and 157 non-depressed control subjects. Subjects were additionally dichotomized based on presence or absence of subcortical MRI lesions and age of onset. Medical comorbidity was assessed by self report only, and depressed subjects were additionally assessed by the clinician-rated Cumulative Illness Rating Scale. RESULTS: When compared with the non-depressed group, depressed subjects were significantly more likely to report the presence of hypertension, heart disease, gastrointestinal ulcers, and 'hardening of the arteries'. Analyses of subjects with subcortical disease demonstrated they were significantly older, more likely to have depression, and more likely to report the presence of hypertension. Finally, the depressed cohort with late-onset depression (occurring after age 50 years) had more male subjects, exhibited greater CIRS scores, and greater prevalence of hypertension, but these did not reach a level of statistical significance after applying a Bonferroni correction. CONCLUSIONS: Vascular comorbidities are common in depressed elders. The differences in the report of hypertension supports past work investigating a vascular contribution to late-life depression. Given the association between depression and poor medical outcomes of cardiac disease, this population deserves clinical scrutiny and further research.

Age Factors↗

PubMed2004

Is there a definition of remission in late-life depression that predicts later relapse?

Remission of depressive symptoms is the goal of all antidepressant therapy. Rating scales define remission in clinical trials, but it is unclear how well these definitions predict risk of later relapse. We measured the sensitivity and specificity of a range of Montgomery-Asberg Depression Rating Scale (MADRS) cutoff scores at 3- and 6-months, wherein scores above a given cutoff would predict relapse over an 18-month period. We examined 153 elderly depressed subjects exhibiting a MADRS < or = 15 after 3 or 6 months of antidepressant therapy. Subjects who subsequently exhibited a MADRS > 15 during the 18-month study period were defined as relapsed. Receiver operating characteristic (ROC) curves were developed and area under the curve (AUC) values calculated for the sensitivity and specificity of 3- and 6-month MADRS scores to predict future relapse. The 3-month ROC had an AUC value of 0.63; the 6-month ROC had an AUC value of 0.66. There was no MADRS cutoff found that could predict likelihood of relapse with good sensitivity and specificity. A post hoc analysis where relapse rate was adjusted by controlling for medical comorbidity, disability, and social support showed no change in the ROCs or AUC values. The higher the MADRS score at 3 and 6 months, the greater the likelihood of relapse. With no clean MADRS cutoff score, the goal of antidepressant therapy should be the lowest possible degree of depressive symptomatology to minimize risk of later relapse. Definitions of remission that are better associated with longer-term outcomes are needed.

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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

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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PubMed2003

Smaller orbital frontal cortex volumes associated with functional disability in depressed elders.

BACKGROUND: Depression is associated with significant functional impairment. Recent evidence has linked the orbital frontal cortex (OFC) with depression. We examined the relationship between OFC volumes in older subjects and impairment in the basic (BADL) and instrumental (IADL) activities of daily living. METHODS: The sample consisted of 81 subjects aged 60 years or older; 41 were depressed subjects and 40 healthy control subjects. In a structured interview, subjects reported their medical history and ability to perform both BADL and IADL. Subjects then had a brain magnetic resonance imaging (MRI) scan; the OFC was manually traced bilaterally using neuroanatomical landmarks. Logistic regression was used to examine the effect of OFC volume on BADL and IADL while controlling for the effects of total brain volume, subject status, medical comorbidity, and demographic factors. RESULTS: Smaller OFC volumes, along with greater cognitive impairment as measured by the Mini-Mental State Examination, were significantly associated with BADL impairment. Smaller OFC volumes and being depressed were significantly associated with IADL impairment. CONCLUSIONS: Smaller OFC volumes are independently associated with functional impairment, supporting its role in depression. Further studies are needed to determine how smaller OFC volumes are related to other MRI abnormalities associated with depression and functional impairment.

Activities of Daily Living↗

PubMed2003

White matter hyperintensity progression and late-life depression outcomes.

CONTEXT: White matter hyperintensities (WMHs) are bright foci seen in the parenchyma of the brain on T2-weighted cranial magnetic resonance imaging (MRI) scans and are associated with geriatric depression. Because they are associated with age, they should increase in number and size over time. To our knowledge, this is the first longitudinal, volumetric MRI study of WMHs in depression. OBJECTIVE: To determine if WMH progression over 2 years influences depression outcomes. DESIGN: Over 2 years, depressed subjects received antidepressant treatment according to a naturalistic somatic treatment algorithm designed to offer the best possible treatment to the individual. After the treatment period, depressed subjects were dichotomized based on whether they had reached and sustained remission during this period. PARTICIPANTS: One hundred thirty-three subjects aged 60 years or older meeting DSM-IV criteria for major depressive disorder. MEASURES: Cranial MRI was obtained at baseline and approximately 2 years later. White matter hyperintensity volume was measured in each hemisphere using a semiautomated segmentation process. OUTCOMES: Subjects were dichotomized based on achieving or not achieving remission of depressive symptoms, defined as a Montgomery-Asberg Depression Rating Scale score of 8 or less. RESULTS: The depressed subgroup that achieved and sustained remission had significantly less increases in WMH volume (11.5%) than did the group that did not achieve or sustain remission (31.6%) (P =.01). In a regression model, greater change in WMH volume was significantly associated with failure to sustain remission (P =.004) even when controlling for baseline depression severity, medical illness severity, age, sex, and race. Education was associated with achieving and sustaining remission (P =.02). CONCLUSIONS: Greater progression of WMH volume is associated with poor outcomes in geriatric depression. Future work is needed to develop means of slowing the rate of WMH progression and to determine whether this will lead to improved depression outcomes in elderly persons.

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PubMed2003

The impact of religious practice and religious coping on geriatric depression.

OBJECTIVE: Both religiousness and social support have been shown to influence depression outcome, yet some researchers have theorized that religiousness largely reflects social support. We set out to determine the relationship of religiousness with depression outcome after considering clinical factors. METHODS: Elderly patients (n=114) in the MHCRC for the Study of Depression in Late Life while undergoing treatment using a standardized algorithm were examined. Patients completed measures of public and religious practice, a modified version of Pargament's RCOPE to measure religious coping, and subjective and instrument social support measures. A geriatric psychiatrist completed the Montgomery-Asberg Depression Rating Scale (MADRS) at baseline and six months. RESULTS: Both positive and negative religious coping were related to MADRS scores in treated individuals, and positive coping was related to MADRS six months later, independent of social support measures, demographic, and clinical measures (e.g. use of electro-convulsive therapy, number of depressed episodes). Public religious practice, but not private religious practice was independently related to MADRS scores at the time of completion of the religiousness measures. Religious coping was related to social support, but was independently related to depression outcome. CONCLUSIONS: Clinicians caring for older depressives should consider inquiring about spirituality and religious coping as a way of improving depressive outcomes.

Adaptation, Psychological↗

PubMed2003

Left orbital frontal cortex volume and performance on the benton visual retention test in older depressives and controls.

Changes within the prefrontal cortex (PFC) have been associated with both mood disorders and with specific impairments in cognitive testing. The left PFC has been implicated in relational processing, that is, binding different pieces of information. We hypothesized that among older depressives and elderly controls, lower performance on one test of relational processing would be associated with smaller volume of the orbital frontal cortex (OFC). A total of 30 depressed and 40 control subjects were included in the study. All subjects were administered the Benton Visual Retention Test (BVRT). Subjects received a standardized magnetic resonance imaging, for which volumes of the OFC and total brain were calculated. We found that, controlling for age and education, total correct on BVRT was associated with left OFC volume normalized for total brain volume among the entire sample. For the depressed sample only, the number of perseverative errors was negatively associated with left OFC volume normalized for total brain volume after controlling for age and education. These results add to the literature linking mood and cognitive disturbances to the PFC. Future studies with a larger sample employing functional measures are warranted.

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PubMed2003

Associations among the NEO Personality Inventory, Revised and the serotonin transporter gene-linked polymorphic region in elders: effects of depression and gender.

OBJECTIVE: The short variant of the serotonin transporter gene-linked functional polymorphic region (5-HTTLPR) has been associated with personality traits related to anxiety, hostility, and depression. We attempted to replicate findings suggesting a positive relation between the short allele variant of 5-HTTLPR and Neuroticism, and a negative association between the short allele variant and Agreeableness. METHODS: Participants in the present study were 103 geriatric depressed patients and 99 non-depressed age matched controls. Depression status and gender were examined as potential modifiers of the association between 5-HTTLPR and personality. RESULTS: Neuroticism was associated with allele frequency such that individuals with the short variant of the allele (ss or sl, group S) were significantly lower on Neuroticism ( P<0.04) compared with individuals with the long allele variant (group L), a pattern opposite to that of previous reports. The association did not vary by clinical group (depressed or controls) but was conditional on gender ( P<0.01): the mean Neuroticism for males in group S was 48.2, whereas the mean Neuroticism for males in group L was 55.9; and the mean Neuroticism for females did not differ by allele group. In the total sample, Agreeableness was not associated with allele frequency; however, there was a significant allele groupxclinical groupxgender interaction ( P<0.01). CONCLUSIONS: The present findings failed to replicate prior work suggesting that the short variant of the 5-HTTLPR allele is associated with higher Neuroticism and lower Agreeableness.

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PubMed2003

Serial MR imaging of volumes of hyperintense white matter lesions in elderly patients: correlation with vascular risk factors.

OBJECTIVE: The purpose of the study was to examine change in volume of hyperintense white matter lesions in a cohort of community-dwelling elderly subjects without neuropsychiatric disease. SUBJECTS AND METHODS. One hundred seventeen volunteers underwent brain MR imaging on a 1.5-T scanner. Demographic data and the presence of specific medical illnesses were recorded at the time of the initial scanning. Hyperintense white matter lesion volume was measured using a supervised semiautomated technique that seeded lesions and then created a segmented lesion image. Subjects underwent repeated MR imaging at a mean of 25 months. Mean change in lesion volume and mean percentage of change were determined between the two time points. Logistic regression models were used to examine the differential effects of age, sex, race, and self-reported medical morbidity. RESULTS: Mean baseline volume of cerebral hyperintense lesions was 4.91 cc, and at 2-year follow-up, it was 6.42 cm(2) (p < 0.0001), for a mean increase of 26.7%. Comparable results were seen in separate analyses of hemispheric hyperintense lesion volumes. Neither sex, race, nor baseline hyperintense lesion volume was significantly associated with an interval increase in lesion volume. Age (p = 0.0117) and presence of diabetes (p = 0.0215) were associated with greater change. CONCLUSION: Elderly subjects exhibited approximately a 27% increase in hyperintense lesion volume over a 2-year period, a finding influenced by both age and medical comorbidity rates. Because hyperintense lesions can be associated with several neuropsychiatric conditions, further research is needed to determine if interventions designed to slow hyperintense lesion disease progression may improve neuropsychiatric outcomes.

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