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OBJECTIVE It is well documented that depression and early mortality are related, and current research suggests that depression may influence vascular causes of death. The authors report on prospectively observed mortality in elderly depressed patients, comparing differences in sex and vascular risk. METHODS The subjects were 338 patients with unipolar major depression; patients with neurological or other psychiatric disorders were excluded. All subjects received a clinical evaluation and a standardized interview to establish DSM-III depression diagnosis. The cohort had a mean age of 67.2 years and was followed up at approximately 10 years from last contact. RESULTS Mortality was associated with older age, older age at depression onset, and being male. Also, in men, mortality was associated with higher baseline CES–D scores, and, in women, with having a higher vascular risk rating or late age at depression onset. CONCLUSION This is the first study demonstrating a gender-by-vascular condition interaction effect on mortality. Women with vascular risk factors may require closer follow-up to control vascular conditions. The relationship between greater depression and increased mortality risk among men is interesting, and further studies will be required to replicate and understand it.

Background:Neuroticism is a psychological construct that includes tendency to exhibit negative affect (NA), having poor stress tolerance and being at risk for depression and anxiety disorders. The consequences of neuroticism in the elderly adults are understudied. We hypothesized that older depressed patients with comorbid neuroticism at baseline would have worse mood and cognitive outcomes compared with older depressed patients without neuroticism.Methods:One hundred and ten older depressed adults completed baseline self-reports of depression and the NEO-Personality Inventory as a measure of neuroticism, were administered a battery of cognitive tests annually and were seen by a study psychiatrist who assessed patients using the Montgomery Åsberg Depression Rating Scale (MADRS) and treated patients with antidepressants using an established treatment guideline. Patients were followed as clinically indicated for up to three years. We measured remission (defined as MADRS score ≤ 6) rates at one year as a categorical outcome. In addition, we used Cox proportional hazard models to examine the relationship between neuroticism and change in MADRS and cognitive score over time.Results:Non-remitters (30%) at one year had higher scores in total neuroticism (TN), vulnerability to stress (VS), and NA. Over three years, time to achieve remission was associated with higher TN, higher VS, and greater NA. In analyses controlling for baseline cognitive score, age, sex, and education, VS was associated with baseline to two-year change in cognition.Conclusions:Presence of neuroticism in older depressed patients treated with medication is associated with poor mood outcomes and may indicate increased risk of cognitive decline.

Major depressive disorder is associated with smaller hippocampal volumes but the mechanisms underlying this relationship are unclear. To examine the effect of environmental influences, we examined the relationship between self-reported stressors and two-year change in hippocampal volume. Seventy elderly nondepressed subjects and eighty-nine elderly depressed subjects were followed for two years. The number of negative stressful life events (nSLE), perceived stress levels, and cranial MRI were obtained at baseline and at the two-year assessment. For secondary analyses, subjects provided blood for 5-HTTLPR polymorphism genotyping. After controlling for covariates including presence or absence of depression, greater numbers of baseline nSLEs were significantly associated with greater baseline hippocampal volumes bilaterally. Greater numbers of baseline nSLEs were also associated with reduction in hippocampal volume over two years in the right but not the left hemisphere. Neither perceived stress levels nor changes in stress measures were significantly associated with hippocampal volume measures. However, in secondary analyses, we found that increases in perceived stress over time was associated with volume reduction of the left hippocampus, but only in 5-HTTLPR L/L homozygotes. Our findings suggest different short- and long-term effects of negative life stressors on hippocampal volumes in older adults. These effects appear independent on the presence or absence of depression. Furthermore, these effects may be moderated by genetic polymorphisms in key neurotransmitter systems. These novel findings have important implications for understanding environmental influences on brain aging.

Although the relation between stressful life events (SLEs) and risk of major depressive disorder is well established, important questions remain about the effects of stress on the course of geriatric depression. Our objectives were (1) to examine how baseline stress and change in stress is associated with course of geriatric depression and (2) to test whether polymorphisms of serotonin transporter (5-HTTLPR) and catechol-O-methyltransferase (COMT Val158Met) genes moderate this relation. Two-hundred and sixteen depressed subjects aged 60 years or older were categorized by remission status (Montgomery-Asberg depression rating scale≤6) at 6 and 12 months. At 6 months, greater baseline numbers of self-reported negative and total SLEs and greater baseline perceived stress severity were associated with lower odds of remission. At 12 months, only baseline perceived stress predicted remission. When we examined change in stress, 12-month decrease in negative SLEs and level of perceived stress were associated with improved odds of 12-month remission. When genotype data were included, COMT Val158Met genotype did not influence these relations. However, when compared with 5-HTTLPR L/L homozygotes, S allele carriers with greater baseline numbers of negative SLEs and with greater decrease in negative SLEs were more likely to remit at 12 months. This study demonstrates that baseline SLEs and perceived stress severity may influence the 12-month course of geriatric depression. Moreover, changes in these stress measures over time correlate with depression outcomes. 5-HTTLPR S carriers appear to be more susceptible to both the effects of enduring stress and the benefit of interval stress reduction.

Objective To explore the relationship between personality, social support, and depression in older adults, identify the personality trait and social support dimension most closely associated with depression, and determine whether the relationship between personality and depression varies by level of social support. Design Cross-sectional analysis within longitudinal study. Participants Older patients originally diagnosed with major depression (n = 108) and never-depressed comparison group of older adults (n = 103). Measurements Patients sufficiently recovered from major depression and comparison participants were administered the NEO Personality Inventory. Social support was measured annually for both groups. Patients were administered the Montgomery-Asberg Depression Rating Scale (MADRS) every 3 months. Results Patients and comparison participants differed on four of the five NEO domains and all four social support dimensions, but personality did not significantly predict depression status (patient/comparison) in controlled analyses. Within the patient group, subjective social support was the only dimension correlated with MADRS score. In separate linear regression analyses among the patients, controlling for age, sex, and subjective social support, the domains of Neuroticism, Openness to Experience, Conscientiousness, and Extraversion were associated with MADRS score. For Neuroticism and Openness, the association varied by level of subjective social support. Conclusions Our research confirmed that older patients differed from never-depressed older adults in dimensions of personality and social support, and the relationship between these variables differed by depression status. The relationship between personality, social support, and depressive symptoms in older adults recovering from depression is also complex, with subjective social support modifying the association between personality and depression.

Background: Cultural biases may affect the individual responses to questionnaires for depression and thus confound the international or multiethnic researches on depression. Objective: We compared the diagnostic accuracy of the Center for Epidemiologic Studies Depression Scale (CES-D) for major depressive disorder (MDD) in late life between Korean and US Caucasian elderly. Methods: This study included 332 US Caucasian MDD patients, 116 Korean MDD patients, 125 US Caucasian nondepressed subjects and 700 Korean nondepressed subjects. Differential item functioning and factor analyses were conducted to examine the differences in the response patterns to the CES-D between the US Caucasian and Korean elderly. Diagnostic accuracy of the CES-D for MDD was compared using the area under the receiver-operating characteristic curves (AUC). Results: The Korean elderly were more likely to endorse 6 items compared to the US Caucasians, and the US Caucasian elderly were more likely to endorse 5 items compared to the Koreans. The factor solutions from both ethnic groups were not comparable since the congruence coefficient for the second factor was below 0.46 and that for the first factor did not reach 0.90. The AUC of the CES-D for MDD in Koreans (AUC = 0.850, 95% CI = 0.801–0.899) was significantly smaller than that in US Caucasians (AUC = 0.973, 95% CI = 0.960–0.987), and the optimal cutoff score of the CES-D in the Korean elderly (21/22) was 2 times higher than that in the US Caucasian elderly (10/11). Conclusion: Cross-cultural issues may significantly influence the diagnostic accuracy of depression questionnaires and thus should be considered more carefully than before in both clinical and research settings on multiethnic populations.

Objective The Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with geriatric depression. In studies of younger adults without depression, met allele carriers exhibit smaller hippocampal volumes and have poorer performance on neuropsychological tests. The authors examined the relationship between the BDNF gene and hippocampal volumes in depressed and nondepressed older individuals and its relationship with memory functions mediated by the hippocampus. Design One hundred seventy-six elderly depressed white participants and 88 nondepressed participants completed clinical assessments, neuropsychological testing, and provided blood samples for genotyping. One hundred seventy-three participants also underwent brain magnetic resonance imaging. Statistical modeling tested the relationship between genotype and hippocampal volume and function while controlling for diagnosis and other covariates. Results BDNF genotype was not associated with a difference in performance on tests mediated by the hippocampus, including word list learning, prose recall, nonverbal memory, or digit span. After controlling for covariates, BDNF genotype was not significantly associated with hippocampal volume ( F [ 1 , 171 ] = 1.10, p=0.30). Conclusion Despite different findings in younger populations, the BDNF Val66Met polymorphism is not significantly associated with hippocampal volume or function in a geriatric population. The authors hypothesize that other factors may have a stronger effect on hippocampal structure in older individuals and that the association between the Val66Met polymorphism and geriatric depression is mediated through other mechanisms.

SUMMARY Objective The objectiveofthe currentstudy wasto examine therelationshipbetween theCOMTVal 158 Metpolymorphism and neuropsychological performance in depressed and nondepressed older adults. Methods One hundred and twenty-six clinically depressed older adults and 105 nondepressed comparison participants were compared on neuropsychological performance and COMT Val 158 Met (Val/Val, Val/Met, Met/Met). Results Based on multivariate regression models, the COMT Val 158 Met polymorphism was not associated with cognitive performance among depressed or nondepressed individuals, nor did this polymorphism account for the fact that depressed individuals performed worse than nondepressed individuals on several neuropsychological tests that are typically affected by depression. There was also no difference in frequency of the COMT Val 158 Met alleles between depressed and nondepressed individuals. Conclusions Although the current study found no association between COMT Val 158 Met polymorphism on a number of clinical neuropsychological tests that are typically found to be sensitive to depression, differential effects of the COMT Val 158 Met polymorphism on dopamine transmission in psychiatric and non-psychiatric populations may be further clarified by clinical research with neuroscience-based paradigms that segregate cognitivetasks into component processes with precise neural substrates, particularly with respect to the complex functions of the prefrontal cortex. Negative results can be important to narrowing down target processes and understanding the influence of clinical and demographic characteristics in studies of psychiatric genetics. Copyright # 2009 John Wiley & Sons, Ltd. key words—geriatric depression; aging; Catechol-0-Methyltransferase; neuropsychology; cognition

Objective—The goal of the current study was to examine the neuropsychological profile of magnetic resonance imaging (MRI)-defined subcortical ischemic depression (SID). Methods—Clinically depressed older adults with MRI-defined SID (n = 70) and depressed elders without SID (n = 75) were compared on neuropsychological performance, depression symptoms and medical burden. Results—Group comparisons revealed that the SID was associated with worse performance on all neuropsychological measures, but also with greater age, higher cardiac illness burden, and greater deficits in the depression symptoms of self-initiation and concentration. In multivariate regression models, auditory working memory and nonverbal memory remained worse among the SID group after controlling for contributions of age, cardiovascular risk, and depression symptoms. Conclusions—Although auditory working memory span and nonverbal memory appear to be specifically associated with the ischemic pathology that defines SID, the typical individual with SID is also likely to have a broader profile of neuropsychological deficits than those without SID because they are typically older and have profiles of depression symptoms that predispose them to compromised neurocognitive performance.

Although often viewed as a purely environmental construct, perception of social support may be influenced by genetic factors. This study examined the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and social support measures in older subjects. The sample consisted of 243 depressed and 115 nondepressed older subjects, age 60 years or older; 233 were Val66 allele homozygotes, while 125 were Met66 allele carriers. All subjects completed clinical assessments, including a self-report questionnaire assessing four social support domains, and provided blood for genotyping. Statistical models examined the relationship between scale scores of social support and BDNF Val66Met genotype, while controlling for presence or absence of major depressive disorder and other demographic factors significantly associated with social support. As social support measures were not normally distributed, log-transformed scores were examined. After controlling for diagnosis and education level, the Met66 allele was associated with lower levels of subjective social support (F(1,357) = 5.33, P = 0.0216) and a trend for fewer social interactions (F(1,357) = 3.66, P = 0.0567). To our knowledge, this is the first report associating a measure of social support with a genetic polymorphism. This supports previous work that genetic factors may influence social support perception. Further work is needed to determine the generalizability of this finding to the broader population, as well as its significance for clinical outcomes.

Objective In animal models, brain-derived neurotrophic factor (BDNF) appears to protect against cerebral ischemia. The authors examined whether the BDNF Val66Met polymorphism, which affects BDNF distribution, was associated with greater volumes of hyperintense lesions as detected on magnetic resonance imaging in a cohort of depressed and nondepressed elders. Design Subjects completed cross-sectional assessments, including clinical evaluation and a brain magnetic resonance imaging scan, and provided blood samples for Val66Met genotyping. Setting The study was conducted at a university-based academic hospital. Participants Participants included 199 depressed and 113 nondepressed subjects aged 60 years or older. Measurement Hyperintensity lesion volumes were measured using a semiautomated segmentation procedure. Statistical models examined the relationship between genotype and lesion volume while controlling for depression, presence of hypertension, age, and sex. Results After controlling for covariates, Met66 allele carriers exhibited significantly greater white matter hyperintensity volumes (F 1,311 = 4.09, p=0.0442). This effect was independent of a diagnosis of depression or report of hypertension. Genotype was not significantly related to gray matter hyperintensity volume (F 1,311 = 1.14, p=0.2871). Conclusions The BDNF Met66 allele is associated with greater white matter hyperintensity volumes in older individuals. Further work is needed to determine how this may be associated with other clinically relevant findings in late-life depression.

Background—Rates of suicide among older adults in the United States are higher than that of other age groups. Therefore, it is critically important to deepen understanding of the processes that drive suicide risk among at-risk older patients. To this end, we examined the longitudinal course of suicide ideation in a sample of treatment-seeking depressed adults 60 years of age or older. Methods—Secondary analyses were conducted with a longitudinal dataset including 343 older adults seeking treatment for depression in the context of a naturalistic treatment setting. Participants completed assessments of depressive symptoms and thoughts of suicide every three months for one year. Multi-level mixed models were used to examine the trajectory of suicide ideation over five waves. Results—Depressive symptoms contributed significantly to change in thoughts of suicide early in treatment for depression. Age-related differences were also observed, such that increasing age was associated with significantly greater reports of suicide ideation. Limitations—Use of a single measure to ascertain severity of depressive symptoms and thoughts of suicide. Conclusions—Clinicians should expect to see the most pronounced decrease in thoughts of suicide during the first two months of depression treatment for older adults. Further, clinicians should be especially vigilant to monitor suicide ideation for adults, with increasing vigilance for those at more advanced ages.

Objective Converging lines of evidence implicate vascular factors in late-life depression, and argue that late-life depression is a distinct entity among the mood disorders. The A1166C polymorphism in the angiotensin II receptor, vascular type 1 (AGTR1) gene has been associated with a range of vascular diseases. This study investigated the association of AGTR1 genotype on 18-month treatment outcome in late-life depression. Methods In a large, prospective cohort study, patients with late-life depression received individualized treatment using a standardized algorithm. The authors genotyped participants at the AGTR1 A1166C single nucleotide polymorphism (SNP) using standardized methodology, then used survival analysis to estimate the impact of A1166C and demographic variables on time to remission during 18 months of follow-up. Results The hazard ratio for AGTR1 homozygous C/C status was 0.37. The A1166C SNP showed evidence for genotypic and allelic association in a comparison of remitted and unremitted/censored subjects. Conclusion Consistent with its association with numerous vascular disorders, AGTR1 is associated with treatment outcome in late-life depression. Further studies are needed to replicate this finding, and to investigate the impact of other genetic markers of vascular disease on late-life depression outcome.

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. Copyright © 2006 John Wiley & Sons, Ltd.

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. Copyright © 2005 John Wiley & Sons, Ltd.

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.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.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.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.

This study sought to examine the effects of taking cholesterol-lowering medication on outcomes of depression among older depressed adults. 243 elderly depressed patients were treated using an antidepressant algorithm by a geriatric psychiatrist who administered the Montgomery-Asberg Depression Rating Scale (MADRS) at clinical visits up to six years. We defined remission and relapse as achieving MADRS scores less than 7 and greater than 15, respectively. There were no between-group differences on time to remission. Among 167 remitted patients with follow-up data, 61.4% on cholesterol-lowering medication, and 39.8% not on cholesterol medications experienced a relapse during the follow-up period (p0.032), and remitted patients taking cholesterol medications relapsed more quickly than did others in adjusted analyses (hazard ratio=1.791, p0.018). These results add to the literature linking cholesterol and mood, and they support the "vascular depression" hypothesis in geriatric depression. Future studies of depression outcomes in the elderly will need to include serial examination of cholesterol levels.

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. Copyright © 2003 John Wiley & Sons, Ltd.

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.Mean baseline volume of cerebral hyperintense lesions was 4.91 cc, and at 2-year follow-up, it was 6.42 cm(2) (p0.0001), 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.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.

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.

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

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.

Although there have been previously published algorithms for the treatment of depression, few have been rigorously studied in terms of outcome. We present the Duke Somatic Treatment Algorithm for Geriatric Depression (STAGED) approach, developed by clinicians in the Duke Mood Disorders Program. The algorithm consists of five stages based on treatment history. In developing the approach, we enrolled 228 depressed elderly patients in a National Institute of Mental Health-funded longitudinal study of depression. Patients were treated by geriatric psychiatrists using the algorithm as a guideline for treatment. Initially, 174 patients were treated with antidepressant medications, and 54 patients were treated with electroconvulsive therapy. Over the course of 18 months of treatment, 88.6% of patients responded, and 65.35% of patients were able to achieve full remission of symptoms. The STAGED approach appears to be a clinically useful method of successfully treating elderly depressed patients.

The authors examined psychosocial and clinical predictors of time-to-remission in a sample of initially clinically depressed elderly patients.Using a standardized algorithm, a prospective cohort study enrolled 239 patients undergoing treatment. Patients were followed for up to 4.5 years, until death or withdrawal from the study. Baseline predictor variables included psychosocial factors, such as four domains of social support; basic and instrumental activities of daily living; and clinical factors, including use of electroconvulsive therapy (ECT), past history of depression, comorbidities, and antidepressant treatment.Only 33% of the sample (n=79) met our classification for depression remission. A lack of instrumental and subjective social support, poor self-rated health, the use of antipsychotic medication, or use of an antidepressant in the last 7 days were predictors of longer time-to-remission. Use of ECT in the last year was related to shorter time-to-remission.Baseline psychosocial factors were just as important, as predictors of depression remission, as were clinical and diagnostic variables. Interventions directed toward social support resources, in addition to clinical intervention, including the use of ECT where appropriate, are likely to improve rates of depression remission.

It is well documented that depression and early mortality are related, and current research suggests that depression may influence vascular causes of death. The authors report on prospectively observed mortality in elderly depressed patients, comparing differences in sex and vascular risk.The subjects were 338 patients with unipolar major depression; patients with neurological or other psychiatric disorders were excluded. All subjects received a clinical evaluation and a standardized interview to establish DSM-III depression diagnosis. The cohort had a mean age of 67.2 years and was followed up at approximately 10 years from last contact.Mortality was associated with older age, older age at depression onset, and being male. Also, in men, mortality was associated with higher baseline CES-D scores, and, in women, with having a higher vascular risk rating or late age at depression onset.This is the first study demonstrating a gender-by-vascular condition interaction effect on mortality. Women with vascular risk factors may require closer follow-up to control vascular conditions. The relationship between greater depression and increased mortality risk among men is interesting, and further studies will be required to replicate and understand it.

Background Biological markers of treatment response may include structural brain changes seen on neuroimaging. While most imaging studies have focused on cerebrovascular disease, evidence is growing that the hippocampus may play a role in depression, particularly geriatric depression. Method We studied 60 depressed elderly patients enrolled in a longitudinal study who were treated with antidepressant medications using a treatment guideline-based approach. Baseline and 12-week Montgomery-Asberg Depression Rating Scale (MADRS) scores were obtained via interview with a geriatric psychiatrist. All subjects had a baseline magnetic resonance imaging (MRI) brain scan. MRI scans were processed using standard protocols to determine total cerebral volume and right and left hippocampal volumes. Hippocampal volumes were standardized for total cerebral volume. MADRS scores less than 10 were used to define remission. Results When the group with the lowest quartile of standardized hippocampal volumes was compared to those above the first quartile, those with small right and total hippocampal volumes were less likely to achieve remission. In a subsequent logistic regression model controlling for age small standardized right hippocampal volumes remained significantly associated with remission. Conclusion Further studies with larger sample are needed to determine if left-right hippocampal volume differences do exist in depression, and basic neuroscience studies will need to elucidate the role of the hippocampus in geriatric depression. Copyright © 2002 John Wiley & Sons, Ltd.

Introduction Bupropion immediate release (IR) and bupropion sustained release (SR) are frequently used to treat geriatric depression, as they have few cardiovascular, gastrointestinal and sexual adverse effects. We sought to examine the efficacy and dosing patterns of bupropion in a naturalistic cohort of elderly subjects with major depression (MD). Methods 31 elderly ( > 60 years) patients with unipolar MD (DSM-IV) who were enrolled in Duke's Mental Health Clinical Research Center for the Study of Depression in Later Life were prescribed bupropion SR or IR, alone or in combination with other antidepressant agents, for 12 weeks. Montgomery–Asberg depression rating scale (MADRS) scores and clinical global impression (CGI) severity scores were used to define response. Results 74% (23/31) of the sample were responders (MADRS

Purpose: To describe death-related planning and preferences for place of death among well elders in a community characterized by a low rate of hospital deaths. Design and Methods: Cross-sectional prevalence survey of independent-living residents ( n 5 219) of a continuing-care retirement community (CCRC) in Central North Carolina characterized by a low rate of hospital deaths. Results: Death-related planning played a part in the decision of 40% of residents to move to the CCRC. A majority of residents reported a clear preference for place of death, and a majority of these preferred to die on the CCRC campus. Most residents wanted to discuss their preferences for place of death with their health care provider. Preferences for place of death appear consistent across age cohorts and are relevant to elders’ long-term care decisions. Implications: Given the striking discrepancy between patients’ preferences for nonhospital deaths and the high prevalence of hospital deaths in the United States, this often-neglected issue should be routinely addressed in end-of-life planning. The CCRC may be a practice model that is particularly compatible with personal preferences for place of death.

Background: There is a growing literature on the importance of hippocampal volume in geriatric depression. Methods: We examined hippocampal volume in a group of elderly depressed patients and a group of elderly control subjects ( N = 66 geriatric depressed patients and 18 elderly nondepressed control subjects) recruited through Duke's Mental Health Clinical Research Center for the Study of Depression in the Elderly. The subjects received a standardized evaluation, including a magnetic resonance imaging scan of the brain. Patients had unipolar major depression and were free of comorbid major psychiatric illness and neurologic illness. Differences were assessed using t tests and linear regression modeling. Results: Accounting for the effects of age, gender, and total brain volume, depressed patients tended to have smaller right hippocampal volume ( p = .014) and left hippocampal volume ( p = .073). Among depressed patients, age of onset was negatively but not significantly related to right hippocampal volume ( p = .052) and to left hippocampal volume ( p = .062). We noted that among subjects with either right or left hippocampal volume of 3 mL or less, the vast majority were patients rather than control subjects. Conclusions: These results support a role for hippocampal dysfunction in depression, particularly in late-age onset depression. Longitudinal studies examining both depressive and cognitive outcomes are needed to clarify the relationships between the hippocampus, depression, and dementia.

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 cm 2 for WMLs and 0.23, 0.30 and 0.34 cm 2 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 cm 2 for WMLs and 0.17, 0.25 and 0.23 cm 2 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.

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-Åsberg 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.