Role In Late-life Depression Research Articles

Late life depression and concepts of aging: an emerging paradigm.

Late life depression (LLD) is an emerging challenge, and recognized as a significant barrier to long-term healthy aging. Viewed within the context of the medical/biological model, advances in brain sciences over the last several decades have led to a deeper understanding of the biology of LLD. These advances in current knowledge include the description of aging brain pathophysiology; the biology and biochemistry of neurotransmitters; the correspondence between changes in neurological structure, function, and neural network; the description of neural, hormonal and inflammatory biomarkers; and identification of typical phenotypic subtypes of LLD. Despite these advances, current treatment of LLD, which remains largely pharmacological with accompanying cognitive and behavioral interventions, has poor success rate for long-term remission among older people. A wider perspective, in keeping with several emerging aging concepts, is suggested as an alternative framework within which to view LLD. A growing body of research supports the important role in LLD of frailty, resilience, intrinsic capacity, and functional integrity. Similarly, important social determinants need to be addressed in the etiology of LLD, rooted largely in negative stereotypes of aging, with consequent repercussions of reduced participation and inclusion, growing social isolation, with loss of identity, meaning and hope. This perspective suggests the importance of a wider integrative conceptualization of depression, set against a background of emerging aging concepts.

The body of evidence of late-life depression: the complex relationship between depressive symptoms, movement, dyspnea and cognition

ABSTRACT Background Physical symptoms play an important role in late-life depression and may contribute to residual symptomatology after antidepressant treatment. In this exploratory study, we examined the role of specific bodily dimensions including movement, respiratory functions, fear of falling, cognition, and physical weakness in older people with depression. Methods Clinically stable older patients with major depression within a Psychiatric Consultation-Liaison program for Primary Care underwent comprehensive assessment of depressive symptoms, instrumental movement analysis, dyspnea, weakness, activity limitations, cognitive function, and fear of falling. Network analysis was performed to explore the unique adjusted associations between clinical dimensions. Results Sadness was associated with worse turning and walking ability and movement transitions from walking to sitting, as well as with worse general cognitive abilities. Sadness was also connected with dyspnea, while neurovegetative depressive burden was connected with activity limitations. Discussion Limitations of motor and cognitive function, dyspnea, and weakness may contribute to the persistence of residual symptoms of late-life depression.

Abstract 125: Enlarged Perivascular Spaces In The Centrum Semiovale Are Associated With Incident Late-life Depression: Framingham Heart Study

Introduction: Perivascular spaces visible on brain MRI (PVS) are considered cerebral small vessel disease (CSVD) markers, possibly reflecting impaired brain fluid and metabolite clearance, and could contribute to depression in old age. This study aims to determine the association of PVS with prevalent and incident depression in the community-based Framingham Heart Study (FHS). Methods: FHS participants free of stroke and dementia with available Center for Epidemiological Studies Depression (CES-D) scale and PVS ratings in the basal ganglia (BG) and centrum semiovale (CSO) were included. Depression was defined as CES-D score≥16 or use of antidepressants. PVS were rated on a scale from I-IV in the BG and CSO using a validated method, with grades III-IV representing high PVS burden. A mixed score was created to describe high burden in the BG and/or CSO (0=no high ePVS burden, 1=high burden in the BG, 2=high burden in the CSO, 3=high burden in both regions). Logistic regression analysis was used to assess the association between PVS in the CSO, BG, and mixed regions and prevalent and incident depression. Models adjusted for age, sex, FSH cohort, time interval between CES-D score and MRI measurements, body mass index, smoking status, prevalent hypertension and diabetes. Results: Among 3815 participants included (mean age 57±14, male 47%), incident depression was observed in 19% over the follow up period ranging from 8 to 15 years subsequent to PVS rating. In multivariable adjusted analyses, high burden PVS in the CSO was associated with incident depression (OR 1.75 [1.18, 2.60], p=0.005). In the mixed score, concurrent high burden PVS in both regions (OR 2.10 [1.13, 3.91], p=0.02) and high burden in the CSO only (OR 1.65 [1.05, 2.58], p=0.03) were associated with incident depression. PVS were not associated with prevalent depression. Conclusion: In conclusion, high PVS burden was associated with incident depression in a community-based sample free of stroke and dementia. The association was predominantly driven by high burden of CSO PVS, suggesting that lobar forms of CSVD may play role in late life depression, possibly reflecting disrupted neuroanatomic circuits involved in mood control, and differing from BG PVS.

Stress Detection using Facial Image for Elderly

Stress plays an important role in late-life depression. It is a natural reaction to various factors which can lead to physiological and behavioural changes in human behaviour and performance. Dependence, ill health, loss of social role and recognition, and a lack of opportunity for creative use of leisure are some of the most common medical and psychological difficulties among the elderly. Automatic stress monitoring reduces the likelihood of health problems and promotes society's well-being. Our project's major goal is to use machine learning and image processing techniques to detect stress in the elderly population. Our system is an improved version of previous stress detection systems that did not include live detection, personal counselling, or stress level notification via a mobile device application. Instead, this system includes live detection and periodic analysis of the person in question, as well as detecting mental stress levels and notifying the person's emergency contact. Our system is primarily targeted at the elderly, but it may also be used by students and IT professionals to manage stress and create a healthy, spontaneous work environment for employees, allowing them to give their best during working hours.

Antidepressants differentially related to 1,25-(OH)₂ vitamin D₃ and 25-(OH) vitamin D₃ in late-life depression.

A low plasma 25-OH vitamin D3 level is a universal risk factor for a wide range of diseases and has also been implicated in late-life depression. It is currently unknown whether the biologically active form of vitamin D, that is, 1,25-(OH)2 vitamin D3, is also decreased in late-life depression, or whether vitamin D levels correlate with specific depression characteristics. We determined plasma 25-OH vitamin D3, 1,25-(OH)2 vitamin D3 and parathormone levels in 355 depressed older persons and 124 non-depressed comparison subjects (age⩾60 years). Psychopathology was established with the Composite International Diagnostic Interview 2.1, together with potential confounders and depression characteristics (severity, symptom profile, age of onset, recurrence, chronicity and antidepressant drug use). Adjusted for confounders, depressed patients had significantly lower levels of 25-OH vitamin D33 (Cohen's d =0.28 (95% confidence interval: 0.07–0.49), P=0.033) as well as 1,25-(OH)2 vitamin D3 (Cohen's d =0.48 (95% confidence interval: 0.27–0.70), P<0.001) than comparison subjects. Of all depression characteristics tested, only the use of tricyclic antidepressants (TCAs) was significantly correlated with lower 1,25-(OH)2 vitamin D3 levels (Cohen's d =0.86 (95% confidence interval: 0.53–1.19), P<0.001), but not its often measured precursor 25-OH vitamin D3. As vitamin D levels were significantly lower after adjustment for confounders, vitamin D might have an aetiological role in late-life depression. Differences between depressed and non-depressed subjects were largest for the biologically active form of vitamin D. The differential impact of TCAs on 25-OH vitamin D3 and 1,25-(OH)2 vitamin D3 levels suggests modulation of 1-α-hydroxylase and/or 24-hydroxylase, which may in turn have clinical implications for biological ageing mechanisms in late-life depression.

Dopamine in Area of Brainstem Linked to Late-Life Depression

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessDopamine in Area of Brainstem Linked to Late-Life DepressionJoan Arehart-TreichelJoan Arehart-TreichelSearch for more papers by this authorPublished Online:6 Dec 2013https://doi.org/10.1176/appi.pn.2013.12a2AbstractLate-life depression is common and often resistant to therapy, but pharmacologic enhancement of dopamine transmission may help in some cases of the illness.ktsdesign/ShutterstockFor some time, there has been reason to believe that the brainstem might play a role in late-life depression. Now, Robert Wilson, Ph.D., a professor of neurological sciences and behavioral sciences at Rush University Medical Center, and his colleagues have tested the hypothesis. And as they reported online October 16 in JAMA Psychiatry, dopaminergic neurons in the ventral tegmental area of the brainstem seem to be implicated in development of late-life depression.The study sample consisted of 124 older individuals from a parent study called the Rush Memory and Aging Project.These individuals had undergone extensive annual clinical evaluations that included a structured medical history, a neurological examination, and neuropsychological tests. None of the subjects was diagnosed with dementia on the basis of these evaluations. During each annual evaluation, these individuals were also tested for depression with the Center for Epidemiological Studies Depression Scale. The cohort lived on average five years after entry into the study, and their depression scores over these years were averaged.After the subjects died, their brains were autopsied. The researchers then used the subjects’ depression evaluation material and brain autopsy material to see whether there were any links between late-life depression and four brainstem areas—the dorsal raphe nucleus, the locus ceruleus, the substantia nigra, and the ventral tegmental area.Specifically, they measured dopamine neurons in the substantia nigra and in the ventral tegmental area. A lower density of dopamine neurons in each nucleus was related to a higher level of depressive symptoms when each nucleus was modeled separately. In contrast, when the two nuclei were modeled together, the effect for the substantia nigra was no longer significant, but the effect for the ventral tegmental area remained so. As for the locus ceruleus, the researchers measured noradrenergic (not dopaminergic) neurons, and for the dorsal raphe nucleus, the researchers measured serotonergic (not dopaminergic) neurons. Neither of these neuron measures was related to depressive symptoms.Thus it appeared that the dopamine system in the ventral tegmental area of the brainstem might play an important role in late-life depression, Wilson and colleagues concluded.The results have clinical implications, Wilson said in an interview with Psychiatric News. “Late-life depression is common and often resistant to therapy. These findings suggest that pharmacologic enhancement of dopamine transmission may be helpful in some cases.”The research was funded by the National Institutes of Health and the Illinois Department of Public Health. ■An abstract of “Brainstem Aminergic Nuclei and Late-Life Depressive Symptoms” is posted at http://archpsyc.jamanetwork.com/article.aspx?articleid=1756815. ISSUES NewArchived

Big Five personality and depression diagnosis, severity and age of onset in older adults

BackgroundPersonality may play an important role in late-life depression. The aim of this study is to examine the association between the Big Five personality domains and the diagnosis, severity and age of onset of late-life depression. MethodsThe NEO-Five Factor Inventory (NEO-FFI) was cross-sectionally used in 352 depressed and 125 non-depressed older adults participating in the Netherlands Study of Depression in Older Persons (NESDO). Depression diagnosis was determined by the Composite International Diagnostic Interview (CIDI). Severity of depression was assessed by the Inventory of Depressive Symptomatology (IDS). Logistic and linear regression analyses were applied. Adjustments were made for sociodemographic, cognitive, health and psychosocial variables. ResultsBoth the presence of a depression diagnosis and severity of depression were significantly associated with higher Neuroticism (OR=1.35, 95% CI=1.28−1.43 and B=1.06, p<.001, respectively) and lower Extraversion (OR=.79, 95% CI=.75−.83; B=−.85, p<.001) and Conscientiousness (OR=.86, 95% CI=.81.−.90; B=−.86, p<.001). Earlier onset of depression was significantly associated with higher Openness (B=−.49, p=.026). LimitationsDue to the cross-sectional design, no causal inferences can be drawn. Further, current depression may have influenced personality measures. ConclusionsThis study confirms an association between personality and late-life depression. Remarkable is the association found between high Openness and earlier age of depression onset.

Involvement of brain-derived neurotrophic factor in late-life depression.

Brain-derived neurotrophic factor (BDNF), one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons, synaptic integrity, and synaptic plasticity. Evidence suggests that BDNF is involved in major depression, such that the level of BDNF is decreased in depressed patients and that antidepressants reverse this decrease. Stress, a major factor in depression, also modulates BDNF expression. These studies have led to the proposal of the neurotrophin hypothesis of depression. Late-life depression is associated with disturbances in structural and neural plasticity as well as impairments in cognitive behavior. Stress and aging also play a crucial role in late-life depression. Many recent studies have suggested that not only expression of BDNF is decreased in the serum/plasma of patients with late-life depression, but structural abnormalities in the brain of these patients may be associated with a polymorphism in the BDNF gene, and that there is a relationship between a BDNF polymorphism and antidepressant remission rates. This review provides a critical review of the involvement of BDNF in major depression, in general, and in late-life depression, in particular.

Social inhibition as a mediator of neuroticism and depression in the elderly

BackgroundA number of factors, such as demographics, cognitive function, personality and interpersonal relationship) play a role in late-life depression. This study investigates the influence of social inhibition on the inverse emotional stability (neuroticism) and depressive symptoms found in elderly Thai people.MethodsIn total, 123 elderly Thais aged 60 years of age or older were tested using the 64-item Inventory of Interpersonal Problems, Symptom Checklist-90, and the 16 Personality Factors Questionnaire. Hierarchical regression and path analyses were performed in order to identify the relationships among these variables.ResultsThe age of the participants ranged from 60 to 93 years old (mean = 71.7; SD = 6.2), and out of the group, 51.2% were male, 56.1% were married and 61.8% were on a low income. The average number of years spent in education among the participants was 7.6 (SD = 5.1). The variables found to be significantly associated with depression were age, intellect, social inhibition and possession of inverse emotional stability (neuroticism). Low levels of emotional stability were most strongly associated with depressive symptoms (standardized regression coefficients −0.29), but this effect was found to be reduced (mediated, to −0.26) by social inhibition. In total, 30% of the total variance could be explained by this model, and there was an excellent statistical fit.ConclusionsThe variables found to be significantly associated with depression were a younger age, as well as lower levels of intellectual skill, social inhibition and inversed emotional stability (neuroticism). It was found that a lack of emotional stability is, along with a younger age, the strongest predictor of depressive symptoms, but can be mediated by social inhibition.

Magnetic Resonance Imaging in Late-Life Depression

Disruption of frontal-subcortical and limbic networks is hypothesized to have a key role in late-life depression (LLD) and can be examined using magnetic resonance imaging (MRI) techniques. Gray matter can be examined using T1-weighted MRI, white matter using T2-weighted MRI and diffusion tensor imaging, and functional connectivity in resting-state networks using functional MRI. Although independent MRI studies have supported gray and white matter abnormalities in frontosubcortical and limbic networks and increased functional connectivity in the default-mode network in depression, no study has concurrently examined gray matter, white matter, and functional connectivity. To examine whether results of different MRI techniques are complementary, multimodal MRI was used to compare gray matter, white matter, and resting-state networks between LLD and control groups. Cross-sectional, case-control, multimodal MRI analysis. University research department. Thirty-six recovered participants with LLD (mean age, 71.8 years) and 25 control participants (mean age, 71.8 years). Gray matter was examined across the whole brain using voxel-based morphometry. Subcortical gray matter structures were also automatically segmented, and volumetric and shape analyses were performed. For white matter analysis, fractional anisotropy, axial diffusivity, and radial diffusivity values were examined using tract-based spatial statistics. For resting-state network analysis, correlation coefficients were compared using independent components analysis followed by dual regression. White matter integrity was widely reduced in LLD, without significant group differences in gray matter volumes or functional connectivity. The present work strongly supports the hypothesis that white matter abnormalities in frontal-subcortical and limbic networks play a key role in LLD even in the absence of changes in resting functional connectivity and gray matter. Factors that could contribute to the lack of significant differences in gray matter and functional connectivity measures, including current symptom severity, medication status, and age of participants with LLD, are discussed.

Imaging and genetics advances in understanding geriatric depression

Over a decade has passed since publication of the vascular depression hypothesis that cerebrovascular disease may predispose, precipitate, or perpetuate some geriatric depressive syndromes (Alexopoulos et al, 1997). This construct has catalyzed much research, largely focused on structural neuroimaging, clinical neuropsychology, and in last few years, genetics and cognitive neuroscience. Recent investigations have combined advanced neuroimaging techniques and genetic analyses to delineate key structural and functional findings in late-life depression (LLD). Vascular brain changes on imaging studies have long been associated with LLD. Genetic analysis of vascular changes is an emerging field, and recent work in older populations has focused on polymorphisms associated with (1) psychiatric disease in younger adults or (2) vascular risk factors. We have previously reported links between BDNF (brain-derived neurotrophic factor) polymorphisms (Taylor et al, 2008) and serotonin transporter-linked polymorphic region (5HTTLPR) polymorphisms (Steffens et al, 2008) and white matter hyperintensity (WMH) volumes, supporting theories that these genes also have a role in LLD. The notion that WMHs are vascular in nature led our group to explore relationships between WMH volume and genes associated with systemic vascular risk. These include renin–angiotensin system genes, such as the angiotensin II receptor, vascular types 1 and 2 (AGTR1 and AGTR2) genes. In addition to reports linking AGTR1 polymorphisms to LLD outcomes, we have also found gender-specific associations between AGTR polymorphisms and WMH progression (Taylor et al, 2009). Similarly, the methylenetetrahydrofolate reductase (MTHFR) gene, another vascular risk gene associated with folate and homocysteine metabolism, may be associated with LLD, and we are examining MTHFR and other genes related to folate metabolism in the occurrence of white matter lesions in LLD. Our studies continue to examine the role of vascular risk genes in LLD, focusing on their influence on brain structure and cognition. Consistent with the vascular depression hypothesis is the notion the LLD is associated with disruption in frontal-striatal circuitry. These abnormalities in the prefrontal cortex, striatum, and frontal-striatal white matter tracks are also likely related to genetic differences. A previous study noted a link between the 5HTTLPR short allele and caudate volume in LLD. We recently reported an interaction between two genes, COMT (catechol-O-methyltransferase) and MTHFR, and putamen volume reduction in LLD (Pan et al, 2009). Identification of genes associated with prefrontal cortical structure and function remains an active area of inquiry. Beyond the vascular depression hypothesis, another avenue of genetic/neuroimaging LLD research examines the observed link between depression and later dementia. The hippocampus is a key structure related to both LLD pathophysiology and increased dementia risk. The APOE gene is associated with both depression and Alzheimer's disease, and APOE genotype has been associated with specific shape differences in geriatric depression (Qiu et al, 2009). Allelic differences in the 5HTTLPR gene have also been associated with hippocampal volume in LLD by several groups. Advances in both neuroimaging technologies and genetic assessment allow us to investigate the pathophysiology of affective disorders. Existing paradigms of vascular depression and depression as dementia risk make LLD ideally suited for future genetic/imaging studies.

Stress and Depression Among the Oldest-Old: A Longitudinal Analysis

Stress and psychosocial resources play a crucial role in late-life depression. While most studies focus on predominantly those who are young-old, this study used a sample aged 85 and older. The authors' study aims to examine three research questions: (1) What are the trajectories of depression and its associated factors such as types of stress and psychosocial resources among the oldest-old? (2) What are the longitudinal relationships among the changes in stress, psychosocial resources, and depressive symptoms? (3) Are the effects of the changes in stress on depression trajectory mediated by changes in psychosocial resources? The study used a convenience sample of 193 community-dwelling elders aged 85 and older with four interviews every six months from 1986 to 1988. Using multilevel modeling analyses, longitudinal results showed that changes in positive life events, daily hassles (worries), and mastery were significantly associated with changes in late-life depression among the oldest-old.

The interplay and etiological continuity of neuroticism, difficulties, and life events in the etiology of major and subsyndromal, first and recurrent depressive episodes in later life.

Stressful life events, long-term difficulties, and high neuroticism are established risk factors for depression. Less is known about their role in late-life depression, how they modify or mediate one another's effects, and whether this differs between major and subsyndromal, first and recurrent episodes. The authors used a prospective case-control design nested in a community survey of elderly subjects that included a measure of neuroticism. They compared 83 survey participants who subsequently developed a depressive episode with 83 randomly selected comparison participants. The authors determined dates of onset, history, and severity of episodes and dates of occurrence and severity of stressful life events and difficulties. Stressful life events did not mediate the effects of high neuroticism and difficulties at onset, possibly because of the uncontrollable nature of common stressful life events in later life. Without both high neuroticism and difficulties, stressful life events did not increase risk. High neuroticism and difficulties increased risk, even without a stressful life event. In the presence of high neuroticism and/or difficulties, the depressogenic effect of stressful life events was substantial, suggesting effect modification. The authors found no evidence to suggest etiological discontinuity between major and subsyndromal episodes. First and recurrent episodes showed a discontinuous pattern of associations. Severe stressful life events had weaker associations, but high neuroticism and mild stressful life events had stronger associations with recurrent than with first episodes. This study demonstrated the usefulness of a dynamic stress-vulnerability model for understanding late-life depression. Evidence was found suggesting etiological discontinuity between first and recurrent but not between major and subsyndromal episodes.

Cerebrovascular disease and late life depression: an age old association revisited.

To examine the relationship between depression and cerebrovascular disease in three distinct settings: depression in established cerebrovascular disease, cerebrovascular disease in established depression and depression in vascular dementia. Medline, EMBASE, PsychLit and PsychInfo databases were scanned to locate relevant articles. Data were also extracted from other articles, cited by those articles generated from the above databases. Using operational criteria, the prevalence of depression is higher than controls only within the first year after stroke, but most studies have not employed control groups. The prevalence of depression in vascular dementia compared with Alzheimer's disease is higher in the majority of studies, but matching for sociodemographic factors and severity of cognitive impairment has been inconsistent. An association between frontal/subcortical cerebrovascular lesions and depression in later life has been observed, but there may be methodological flaws underlying this observation in some computerized tomography studies. There is some evidence that cerebrovascular disease has an aetiopathological role in late life depression. The increased likelihood of damage to frontal/subcortical brain circuitry following stroke, transient ischaemia and hypertension may explain the high prevalence of depression in older people with vascular risk factors. More valid definitions of lesion location and the use of appropriately matched control groups would seek to clarify this issue. The extrapolation to care settings from the high prevalence of depression accompanying cerebrovascular disease and the prolongation of disability in depressed people with stroke, suggests closer liaison between old age psychiatrists, neurologists and physicians caring for the elderly.