Elderly Depressed Subjects Research Articles

Depression and Pseudodementia: Decoding the Intricate Bonds in an Italian Outpatient Setting.

In spite of the uncertainties of its diagnostic framework, pseudodementia may be conceptualized as a condition characterized by depressive symptoms and cognitive impairment in the absence of dementia. Given the controversies on this topic, the aim of the present study was to assess neurological and cognitive dysfunctions in a sample of elderly depressed subjects, and the eventual relationship between cognitive impairment and depressive symptoms. Fifty-seven elderly depressed outpatients of both sexes were included in the study. A series of rating scales were used to assess diagnoses, depressive and cognitive impairment. Comparisons for continuous variables were performed with the independent-sample Student's t-test. Comparisons for categorical variables were conducted by the χ2 test (or Fisher's exact test when appropriate). The correlations between between socio-demographic characteristics and clinical features, as well as between cognitive impairment and depressive symptoms were explored by Pearson's correlation coefficient or Spearman's rank correlation. Our data showed the presence of a mild-moderate depression and of a mild cognitive impairment that was only partially related to the severity of depression. These dysfunctions became more evident when analyzing behavioral responses, besides cognitive functions. A high educational qualification seemed to protect against cognitive decline, but not against depression. Single individuals were more prone to cognitive disturbance but were similar to married subjects in terms of the severity of depressive symptoms. Previous depressive episodes had no impact on the severity of depression or cognitive functioning. Although data are needed to draw firm conclusions, our findings strengthen the notion that pseudodementia represents a borderline condition between depression and cognitive decline that should be rapidly identified and adequately treated.

Different Sides of Depression in the Elderly: An In-depth View on the Role of Aβ Peptides.

Late-onset depression (LOD) is the most common neuropsychiatric disorder associated with Alzheimer's disease (AD), often associated with structural and functional brain changes, neuropsychological impairments and negative family history for affective disorders. LOD could be a risk factor or a prodromal phase of AD; this has led to the investigation of the link between depression and amyloid-β (Aβ) peptides by measuring Aβ levels in plasma, cerebrospinal fluid (CSF) and brains of elderly depressed subjects. This study aims to clarify the complex relationship between depression, Aβ peptides and AD. We evaluated all articles published up to 2019 in PubMed in which Aβ was measured in serum (or plasma), CSF or brain in elderly with Major Depressive Disorder or depressive symptoms evaluated with standard scales. Low plasma Aβ42 levels are strongly associated with depression severity. Plasma Aβ40 levels are higher in younger depressed, drug-resistant and those with more severe symptoms. CSF Aβ42 levels are lower in depressed than controls. PET-detected global and region-specific increases in Aβ deposition are sometimes associated with LOD, cognitive impairment, anxiety but not with Cardiovascular Diseases (CVDs)/CVD risk factors. Elderly depressed with CVDs/CVD risk factors have more frequently high plasma Aβ40 levels and drug-resistance; those without Conclusion: Two specific Aβ profiles emerge in the depressed elderly. One is associated with Aβ42 reductions in plasma and CSF, possibly reflecting increased brain amyloid deposition and prodromal AD. The other one is characterized by high plasma Aβ40 levels, cerebrovascular disease and is clinically associated with increased AD risk.

Event-related potential and neuropsychological function in depressed older adults with cognitive impairment: Acorrelational study.

BackgroundIncreased depression severity has been linked to cognitive functioning impairment, such as deficits in episodic memory and executive function, causing difficulties in planning strategies, which ultimately lead to impaired decision‐making functions. There are number of ways to assess cognitive functions, two most important and routinely done tests are neuropsychological test battery (NBT) and event‐related potentials (ERPs).ObjectiveThis study examines the relationship between conventional neuropsychological tests assessing various cognitive domains and an ERP‐P300 in depressed older adults.MethodsForty‐six depressed elderly subjects participated in the study. NBT (Pennsylvania's Penn Computerized Neurocognitive Battery [Penn CNP]) assessing attention, episodic memory, working memory, social cognition, complex cognition, and sensorimotor speed and ERP‐P300 (amplitude μV and latency ms) was recorded using an auditory oddball paradigm.ResultsCorrelation test was run and Pearson’s analysis and revealed that there was a negative statistically significant linear correlation between working memory on NBT and P300 wave amplitude on ERP‐P300 (r = −0.34, P = 0.021) and between complex cognition on NBT and P300 wave latency on ERP‐P300 (r = −0.47, P < 0.001). No correlation was found between other tests on NBT and ERP‐P300 wave characteristics. Further, the regression analysis (R 2) revealed that P300 amplitude was found to significantly predict the working memory (R 2 = 0.116) and P300 latency was found to significantly predict the complex cognition (R 2 = 0.224).ConclusionTherefore, we conclude that neurophysiological measurements cannot be substituted by neuropsychological tests or vice versa; rather, higher brain functions should be estimated by both of the methods.

The effects of cerebral amyloidopathy on regional glucose metabolism in older adults with depression and mild cognitive impairment while performing memory tasks.

Co-occurring depression and mild cognitive impairment (MCI) in older adults are important because they have a high risk of conversion to dementia. In the present study, task-related F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) was used to analyse older adults with concomitant depression and MCI. We recruited 20 older adults with simultaneous depression and MCI and 10 older adults with normal cognition (NC). The Verbal Paired Associates test and digit span test were used for the task-related FDG-PET. The 20 older adults with depression and MCI were classified into two groups based on the F-18 florbetaben PET results: depressed MCI patients with (LLD-MCI-A[+]; n = 11) and without amyloid accumulation (LLD-MCI-A[-]; n = 9). Reduced regional cerebral glucose metabolism (rCMglc) in the left superior frontal region was observed in the LLD-MCI-A(-) group compared with the NC group. Analyses of the NC and LLD-MCI-A(+) groups showed significantly decreased rCMglc in the right inferior parietal and left middle frontal regions in the LLD-MCI-A(+) group. rCMglc in the left precuneus was lower in the LLD-MCI-A(+) group than in the LLD-MCI-A(-) group. Significant correlations between the rCMglc in the right inferior parietal/left precuneus regions and memory task scores were observed based on correlation analyses of NC and LLD-MCI-A(+) groups. The findings in the present study indicate the presence of amyloid accumulation influences glucose metabolism in depressed elderly subjects with MCI while performing cognitive tasks. Task-related FDG-PET examinations may help differentiate MCI associated with depression from comorbid depression in patients with prodromal Alzheimer's disease.

Lower regional gray matter volume in the absence of higher cortical amyloid burden in late-life depression

Late-life depression (LLD) is associated with a risk of developing Alzheimer’s disease (AD). However, the role of AD-pathophysiology in LLD, and its association with clinical symptoms and cognitive function are elusive. In this study, one hundred subjects underwent amyloid positron emission tomography (PET) imaging with [18F]-flutemetamol and structural MRI: 48 severely depressed elderly subjects (age 74.1 ± 7.5 years, 33 female) and 52 age-/gender-matched healthy controls (72.4 ± 6.4 years, 37 female). The Geriatric Depression Scale (GDS) and Rey Auditory Verbal Learning Test (RAVLT) were used to assess the severity of depressive symptoms and episodic memory function respectively. Amyloid deposition was quantified using the standardized uptake value ratio. Whole-brain voxel-wise comparisons of amyloid deposition and gray matter volume (GMV) between LLD and controls were performed. Multivariate analysis of covariance was conducted to investigate the association of regional differences in amyloid deposition and GMV with clinical factors, including GDS and RAVLT. As a result, there were no significant group differences in amyloid deposition. In contrast, LLD showed significant lower GMV in the left temporal and parietal region. GMV reduction in the left temporal region was associated with episodic memory dysfunction, but not with depression severity. Regional GMV reduction was not associated with amyloid deposition. LLD is associated with lower GMV in regions that overlap with AD-pathophysiology, and which are associated with episodic memory function. The lack of corresponding associations with amyloid suggests that lower GMV driven by non-amyloid pathology may play a central role in the neurobiology of LLD presenting as a psychiatric disorder.Trial registration: European Union Drug Regulating Authorities Clinical Trials identifier: EudraCT 2009-018064-95.

Psychosocial factors associated with frailty in the community-dwelling aged population with depression. A cross-sectional study

ObjectiveThere is a two-way relationship between frailty and depression, but the mechanisms by which one may influence the other are not well understood. The objective of this study was to evaluate the relationship between psychosocial factors and frailty in community-dwelling aged populations with depression. DesignObservational cross-sectional study. Site5 primary care centres. ParticipantsCommunity-dwelling subjects with depression aged ≥70 years. Main measurementsFrailty status was established according to Fried criteria, depression and depression severity were evaluated by DSM-IV criteria and the Hamilton Depression Rating Scale, respectively, and psychosocial factors were assessed using the Gijón Social-Familial Evaluation Scale and ad hoc questionnaires. ResultsRecruited were 338 subjects (mean age 77.2 years), 82% women and 36.1% rated as frail. A dose–response relationship was observed between depression severity and frailty risk. Widowhood was a risk factor for frailty, while a higher educational level, home internet, stairs in the home, and an active social life had a protective effect. A multivariate analysis showed that age, number of drugs, and depression severity were independent risk factors for frailty, while an active social life was a protective factor. The severity of depressive symptoms showed higher association with frailty than other clinical and socio-demographic characteristics. ConclusionsIn depressed elderly subjects, frailty is associated with psychologiocal factors such as the intensity of depressive symptoms and with social factors such as education level, widowhood, loneliness, and limited social life. More research is required to better understand the modifiable psychological risk factors for frailty.

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English

Impact on the risk of malnutrition and depression of a clinical trial with nutritional educational intervention in non-institutionalized elderly subjects receiving a telecare service in Terrassa (Spain)

Introduction: the elderly are a growing and vulnerable population. Depression and malnutrition are frequent, and there seems to be associated. Objectives: to assess the impact of a nutritional educational intervention on the risk of malnutrition and depression in elderly subjects. Methods: Analytical, experimental, randomized longitudinal study in 38 autonomous, non-institutionalized elderly subjects. Nutritional and depression risk were measured using the Mini Nutritional Assessment (MNA) and the Yesavage Geriatric Depression Scale (GDS-SF), respectively. The impact of the intervention was measured with nutrition and food security questionnaires. Statistics were performed with Spearman's correlation coefficient, and comparisons between means with the Student's t-test. A p-value  0.05 was considered significant. Results: 63.2 % of the sample had a good nutritional status, 28,9 % were at risk of malnutrition, and 7.9 % had malnutrition. Of the total of participants, 28.9 % had depression. A statistically significant, moderate and negative linear relationship was found between depression and nutritional risk (rho = -0.489; p  0.01). The nutritional educational intervention produced a significant increase in knowledge of food security (2.95 ± 2.53 compared to 0.37 ± 1.46; p  0.0005). Conclusions: the risks of malnutrition and depression are significantly associated in older adults. Furthermore, the nutritional educational intervention improved knowledge of food safety, but did not improve nutritional status or in the degree of depression.

Plasma redox and inflammatory patterns during major depressive episodes: a cross-sectional investigation in elderly patients with mood disorders.

While both depression and aging have been associated with oxidative stress and impaired immune response, little is known about redox patterns in elderly depressed subjects. This study investigates the relationship between redox/inflammatory patterns and depression in a sample of elderly adults. The plasma levels of the advanced products of protein oxidation (AOPP), catalase (CAT), ferric reducing antioxidant power (FRAP), glutathione transferase (GST), interleukin 6 (IL-6), superoxide dismutase (SOD), total thiols (TT), and uric acid (UA) were evaluated in 30 patients with mood disorders with a current depressive episode (depressed patients, DP) as well as in 30 healthy controls (HC) aged 65 years and over. Subjects were assessed with the Hamilton Depression Rating Scale (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Geriatric Depression Rating Scale (GDS), the Scale for Suicide Ideation (SSI), the Reason for Living Inventory (RFL), the Activities of Daily Living (ADL), and the Instrumental Activity of Daily Living (IADL). DP showed higher levels than HC of AOPP and IL-6, while displaying lower levels of FRAP, TT, and CAT. In the DP group, specific correlations were found among biochemical parameters. SOD, FRAP, UA, and TT levels were also significantly related to psychometric scale scores. Specific alterations of redox systems are detectable among elderly DP.

Complement component 3 levels in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder.

Late-life major depression (LLMD) is a risk factor for the development of mild cognitive impairment and dementia, including Alzheimer’s disease (AD) and vascular dementia. Immune dysregulation and changes in innate immune responses in particular, have been implicated in the pathophysiology of both LLMD and AD. Complement system, a key component of the innate immune mechanism, is known to play an important role in synaptic plasticity and cognitive functions. However, its role in LLMD remains unknown. In the present study, we examined the levels of complement component 3 (C3, the convergence point of all complement activation pathways) in the cerebrospinal fluid (CSF) of elderly depressed subjects compared to healthy controls; as well as the relationship of CSF C3 levels with amyloid-beta (Aβ42 and Aβ40), total tau (T-tau) and phosphorylated tau (P-tau) proteins and cognition scores. CSF was obtained from 50 cognitively intact volunteers (major depression group, N = 30; comparison group, N = 20) and analyzed for levels of C3 by ELISA. C3 levels were marginally lower in the major depression group relative to the comparison group. We did not find any significant association of C3 with the AD biomarkers Aβ42 reflecting plaque pathology, P-tau related to tau pathology or the neurodegeneration biomarker T-tau. In contrast, C3 was positively correlated with CSF Aβ40, which may reflect Aβ deposition in cerebral vessel walls. We observed a negative correlation between C3 levels and Total Recall on the Buschke Selective Reminding Test (BSRT) for memory performance in the depressed subjects when controlling for education. This initial evidence on C3 status in LLMD subjects may have implications for our understanding of the pathophysiology of major depression especially in late life.

Cortisol and Quality of Life Responses to Endurance Versus Resistive Exercises in Young Depressed Elderly

AbstractObjective: To compare the effect of endurance versus resistive exercise on cortisol and its reflect on quality of life and depression scale in young depressed elderly.Background: Exercise has been suggested to be a viable treatment for depression. This study compared the effect of endurance versus resistive exercise on cortisol and its reflect on quality of life and depression scale in young elderly in order to help elderly to be more active.Subject and Methods: Thirty subjects (13 men, 17 women) were randomly assigned into two groups equal in number. Group (A) Fifteen subjects (7 men, 8 women) received Mod-erate intensity endurance (aerobic) exercise (50 to 70) % of their maximum heart rate. Group (B) Fifteen subjects (6 men, 9 women) received resistance exercise composed of 6 stations of weight lifting with moderate intensity (30% to 40% of 1 RM for upper body exercises and 50% to 60% of 1 RM for lower body exercise). The program duration for both groups was 3 times/week for 12 weeks.Results: Showed that 12 weeks of endurance or resistance exercise for depressed young elderly subjects caused a statis-tical significant improvement in Hamilton Depression Scale (16.86% for Group A and 17.97% for Group B) and Older People Quality of Life Questionnaire (29.94% for Group A and 20.37% for Group B) and a significant decrease in cortisol level (20.81% for Group A and 15.6% for Group B) at the end of rehabilitation program with the favor of aerobic regard-ing cortisol level and quality of life. On the other hand resistive exercise has more effect on Hamilton Depression Scale.Conclusions: Both endurance and resistance exercise are effective non-pharmacological adjuvant treatment for depres-sion and improvement of quality of life in young elderly.

The Effect of Aging in Inhibitory Control of Major Depressive Disorder Revealed by Event-Related Potentials.

Elderly depressed patients manifest pronounced executive dysfunction compared with younger subjects with depressive disorder. Aging-related brain changes may result in executive dysfunction in geriatric depression. We investigated the neural correlates of inhibitory control processing in depressed subjects at different ages using event-related potentials (ERPs). A equiprobable visual Go/Nogo task was used in 19 young (27.4 ± 5.0 years) and 18 elderly (70.8 ± 6.9 years) depressed subjects and their age-matched healthy controls (20 young subjects, 26.2 ± 3.7 years, and 18 elderly subjects, 68.1 ± 4.8 years). The responses were based on two types of equilateral triangular figures of upright (Go) and inverted triangle (Nogo). The elderly subjects exhibited later N2 and P3 latencies, and larger Go-N2 and P3 amplitudes, compared with the younger subjects. Further, the elderly controls displayed smaller P3 in the central and parietal regions, and yielded larger Nogo-P3 amplitude in the frontal region compared with younger controls. While the young depressed patients yielded smaller P3 amplitude than the controls across frontal, central and parietal regions, elderly depressed patients yielded smaller P3 than the elderly controls only in the frontal region. Our results suggest that the inhibitory control subprocesses are differentially affected by depression and aging. The stimulus response speed and the effort intensity of inhibition control are specifically impaired in the elderly depressed patients. And the diminished amplitudes of frontal P3 in the elderly depression imply a frontal dysfunction mechanism.

State-dependent altered connectivity in late-life depression: a functional near-infrared spectroscopy study

There is a large body of evidence showing a substantial relationship between depression and deficits in cognitive functioning. Especially in late-life depression, cognitive impairments are associated with worse treatment progress and are considered a risk factor for neurodegenerative disorders. However, little is known about the differences in neural processing and coupling during rest and cognitive functions in patients with late-life depression compared to healthy elderly individuals. The study at hand aims to investigate the cognitive control network in late-life depression during a cognitive task and at rest by means of functional near-infrared spectroscopy. Hemodynamic responses were measured at rest and during the Trail Making Test using functional near-infrared spectroscopy in a matched sample of 49 depressed and 51 nondepressed elderly subjects (age range: 51–83 years; 64.1 ± 6.58 [mean ± standard deviation]). Functional connectivity (FC) and network metrics were derived from the data and analyzed with respect to differences between the subject groups. Depressed and nondepressed subjects showed significant differences in FC both at rest and during task performance. Depressed subjects showed reduced FC in a left frontopolar cortical network during task performance and increased FC in a left frontoparietal cortical network at rest. Depressed elderly subjects showed altered FC and network organization during different mental states. Higher FC at rest may be an indicator of self-referential processes such as rumination that may reduce FC during task performance due to an overtaxed executive control system.

Mutual Reciprocal Relationship between Ego Integrity and Depression in Elderly: Multi-dimensional Influencing Factors

Purpose: This study was conducted to examine the mutual reciprocal relationship between elders’ ego integrity and depression including physical and psycho-social predictors of both variables. The study also investigated the significant predictors of elders’ ego integrity and depression. Methods: Data were collected using a structured questionnaire from 137 elders. Results: Perceived health status, self-esteem, family interaction, and depression were significant predictors of ego integrity, whereas pain, self-esteem, and ego integrity were significant factors of depression. The results also showed that ego integrity and depression had reciprocal relationship with each other. Conclusion: Psycho-social factors might be more important to improve ego integrity and to alleviate depression in elderly subjects than physical factors.

Cerebral ABC Transporter-common Mechanisms May Modulate Neurodegenerative Diseases and Depression in Elderly Subjects

In elderly subjects, depression and dementia often coincide but the actual reason is currently unknown. Does a causal link exist or is it just a reactive effect of the knowledge to suffer from dementia? The ABC transporter superfamily may represent a causal link between these mental disorders. Since the transporters ABCB1 and ABCC1 have been discovered as major β-amyloid-exporting molecules at the blood-brain barrier and ABCC1 was found to be directly activated by St. John's wort (SJW), depression and dementia certainly share an important pathophysiologic link. It was recognized that herbal anti-depressant formulations made from SJW are at least as effective for the treatment of unipolar depression in old age as classical pharmacotherapy, while having fewer side effects (Cochrane reports, 2008). SJW is known to activate various metabolizing and transport systems in the body, with cytochrome P450 enzymes and ABC transporters being most important. Does the treatment of depression in elderly subjects using pharmacological compounds or phytomedical extracts target a mechanism that also accounts for peptide storage in Alzheimer's disease and perhaps other proteopathies of the brain? In this review we summarize recent data that point to a common mechanism and present the first promising causal treatment results of demented elderly subjects with distinct SJW extracts. Insufficient trans-barrier clearance may indeed present a common problem in all the proteopathies of the brain where toxic peptides are deposited in a location-specific manner. Thus, activation of efflux molecules holds promise for future treatment of this large group of devastating disorders.

The salience network in the apathy of late-life depression.

Apathy is prevalent in late-life depression and predicts poor response to antidepressants, chronicity of depression, disability, and greater burden to caregivers. However, little is known about its neurobiology. Salience processing provides motivational context to stimuli. The aim of this study was to examine the salience network (SN) resting-state functional connectivity (rsFC) pattern in elderly depressed subjects with and without apathy. Resting-state functional MRI data were collected from 16 non-demented, non-MCI, elderly depressed subjects and 10 normal elderly subjects who were psychotropic-free for at least 2 weeks. The depressed group included 7 elderly, depressed subjects with high comorbid apathy and 9 with low apathy. We analyzed the rsFC patterns of the right anterior insular cortex (rAI), a primary node of the SN. Relative to non-apathetic depressed elderly, depressed elderly subjects with high apathy had decreased rsFC of the rAI to dorsal anterior cingulate and to subcortical/limbic components of the SN. Depressed elderly subjects with high apathy also exhibited increased rsFC of the rAI to right dorsolateral prefrontal cortex and right posterior cingulate cortex when compared to non-apathetic depressed elderly. Elderly depressed subjects with high apathy display decreased intrinsic rsFC of the SN and an altered pattern of SN rsFC to the right DLPFC node of the central executive network when compared to elderly non-apathetic depressed and normal, elderly subjects. These results suggest a unique biological signature of the apathy of late-life depression and may implicate a role for the rAI and SN in motivated behavior.

Effects of escitalopram on serum BDNF levels in elderly patients with depression: a preliminary report

Increasing evidence in the literature suggests a link between the brain-derived neurotrophic factor (BDNF) system and adult depression, supporting a role in the pathophysiology of the disease and response to therapy. Few studies have reported BDNF serum levels in elderly depressed subjects and their relationship with antidepressant therapy. The aim of the study was to evaluate BDNF serum levels in naive elderly depressed patients, before and after antidepressant treatment. We enrolled n = 5 elderly naive patients affected by depression, according to the Diagnostic and Statistical Manual of Mental Disorders-IV Text Revision criteria for major depressive episode. BDNF serum levels were evaluated through ELISA method. Cognitive functions were examined by Mini Mental State Examination (MMSE) and severity of depression was assessed by Geriatric Depression Scale (GDS). BDNF levels were measured at baseline (T0) and after 2 months (T2) of escitalopram. Ten healthy elderly subjects were enrolled as a control group. The serum BDNF levels in patients (T0) and controls were 11.5 ± 0.6 and 13.6 ± 3.4 ng/ml (m ± SD), respectively. At T2, the patients showed a significant improvement of depressive symptoms (p < 0.05), with a not significant increase of MMSE. The serum BDNF concentrations increased to 16.0 ± 2.7 ng/ml at T2 (p < 0.05), beyond the levels of BDNF in controls. The increase in BDNF levels was significantly related to the improvement in GDS scores of the patients (r = 0.9, p < 0.05). Serum BDNF levels may be considered as a marker of response to antidepressant treatment for depression in the elderly.

Serum S100B Represents a New Biomarker for Mood Disorders

Recently, mood disorders have been discussed to be characterized by glial pathology. The protein S100B, a growth and differentiation factor, is located in, and may actively be released by astro- and oligodendrocytes. This protein is easily assessed in human serum and provides a useful parameter for glial activation or injury. Here, we review studies investigating the glial marker S100B in serum of patients with mood disorders. Studies consistently show that S100B is elevated in mood disorders; more strongly in major depressive than bipolar disorder. Consistent with the glial hypothesis of mood disorders, serum S100B levels interact with age with higher levels in elderly depressed subjects. Successful antidepressive treatment has been associated with serum S100B reduction in major depression, whereas there is no evidence of treatment effects in mania. In contrast to the glial marker S100B, the neuronal marker protein neuron-specific enolase is unaltered in mood disorders. Recently, serum S100B has been linked to specific imaging parameters in the human white matter suggesting a role for S100B as an oligodendrocytic marker protein. In sum, serum S100B can be regarded as a promising in vivo biomarker for mood disorders deepening the understanding of the pathogenesis and plasticity-changes in these disorders. Future longitudinal studies combining serum S100B with other cell-specific serum parameters and multimodal imaging are warranted to further explore this serum protein in the development, monitoring and treatment of mood disorders.

Negative life stress and longitudinal hippocampal volume changes in older adults with and without depression

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.

Reduced Serum Nerve Growth Factor in Patients With Late-Life Depression

Nerve growth factor (NGF) is one of the most abundant neurotrophic factors in the central nervous system and has been involved in several neuropsychiatric disorders. We recruited 77 age- and gender-matched elderly subjects (38 with late-life depression, 17 with previous major depressive episode, and 22 healthy subjects in the comparison group). Serum concentration of NGF was determined by enzyme-linked immunosorbent assay. NGF levels were significantly reduced in the depressed patients (p = 0.002) as compared with healthy elderly controls. Elderly control subjects with previous depressive episode also showed a significant reduction in NGF levels as compared with controls (p <0.01); NGF levels were similar between patients with current depressive episode and previous depressive episode (p = 0.2). The present findings provide additional evidence to the relevance of reduced neurotrophic support in the pathophysiology of late-life depression. Also, reduced serum NGF level may be a state marker of depression in elderly subjects.