Neurobiology Of Late-Life Depression Research Articles

The need to change: Is there a critical role of midlife adaptation in mental health later in life?

Although late-life depression (LLD) is a serious health problem and more common than dementia in people over 60, it is underdiagnosed and undertreated. The cognitive-emotional etiology of LLD is particularly poorly understood. This is in contrast to the now extensive literature from psychology and cognitive neuroscience on the characteristics of emotionally healthy aging. This research consistently shows a change in emotional processing in older adults that is modulated by prefrontal regulation. Lifespan theories explain this change in terms of neurocognitive adaptation to limited opportunities and resources that typically occur in the second half of life. Epidemiological data on an increase in well-being after a low point around age 50 suggest that the majority of people seem quite capable of making this adaptation, even though empirical evidence for a causal modulation of this so called 'paradox of aging' and for the role of the midlife dip is still lacking. Intriguingly, LLD is associated with deficits in emotional, cognitive, and prefrontal functions similar to those shown to be crucial for healthy adaptation. Suspected causes of these deficits, such as white matter lesions or affective instability, become apparent as early as midlife when internal and external changes as well as daily challenges set in. Based on these findings, we propose that some individuals who develop depression at older ages may not have been able to successfully implement self-regulatory adaptation at midlife. Here, we review the current evidence and theories on successful aging, the neurobiology of LLD, and well-being across the lifespan. Drawing on recent advances in lifespan theories, emotion regulation research, and cognitive neuroscience, we propose a model of successful versus unsuccessful adaptation that emphasizes the increasing need for implicit habitual control and resource-based regulatory choice during midlife.

Effects of Longitudinal Changes in Neuroticism and Stress on Cognitive Decline

ObjectiveThe relationships among depression, personality factors, stress, and cognitive decline in the elderly are complex. Depressed elders score higher in neuroticism than nondepressed older individuals. Independently, the presence of neuroticism and the number of stressful life events are each associated with worsening cognitive decline in depressed older adults. Yet little is known about combined effects of changes in neuroticism and changes in stress on cognitive decline among older depressed adults. DesignLongitudinal observational study. SettingAcademic Health Center. ParticipantsThe authors examined 62 participants in the Neurobiology of Late-life depression (NBOLD) study to test the hypothesis that, compared with older depressed subjects who experience improved neuroticism and lower psychosocial stressors over time, those with worsening neuroticism and greater psychosocial stressors will demonstrate more cognitive decline. MeasurementsThe authors measured neuroticism using the NEO-Personality Inventory-Revised at baseline and 1 year. Study psychiatrists measured depression using the Montgomery-Ǻsberg Depression Rating Scale. At annual assessments, subjects reported the number of psychosocial stressors in the prior year and completed a neuropsychological evaluation. Participants completed a detailed neuropsychological battery at baseline and annually over 3 years. The battery included a test of delayed story memory (Logical Memory-2 or LMII). The outcome 3-year change in cognitive scores was regressed against 3-year change scores of neuroticism and number of psychosocial stressors, plus their interaction, while adjusting for sex, age, race, education, baseline cognitive score, and 3-year change in MADRS score as covariates. ResultsIn multivariable linear regression analysis with the above covariates, the interaction effect of 3-year change in Total Neuroticism score and 3-year change in Total Stressors on change in LMII performance was statistically significant (B = −0.080[95%CL: −0.145 to −0.015], T = −2.48, df = 52, p = 0.017). Further exploration of this finding showed that 1) when total stressors increased by 2 or more over 3 years, LMII change was inversely associated with neuroticism change; and 2) when neuroticism improved less, LMII change score was inversely associated with total stressor change. There were no other significant interactions between stress and neuroticism on cognition. ConclusionOur findings document the importance of tracking change in neuroticism and monitoring psychosocial stress over the long-term course of treatment in geriatric depression. Both factors exert important combined effects on memory over time. Future studies in larger samples are needed to confirm our results and to extend them to examine both cognitive change and development of dementia.

Exploring relationships between neuroticism, depression, and the progression of cognitive decline over time

<h3>Introduction</h3> Cognitive decline is prevalent in older adults, and predicting onset of cognitive decline in patients is a significant challenge for physicians. Studies have shown a relationship between neuroticism and the onset of cognitive decline in a ten-year time span, and have identified one aspect of neuroticism (N6 – vulnerability to stress) to be specifically elevated in those who later develop cognitive impairment. However, little is known about the onset of cognitive decline in a shorter time span, or if other aspects of neuroticism might be predictors. In addition, the effects of depression in this relationship have yet to be determined. The purpose of this study is to evaluate the relationship between the various facets of neuroticism and the onset of cognitive decline in a 1 to 3 year time span in the presence and absence of depression in a cohort of elderly subjects. <h3>Methods</h3> This is a retrospective cohort study. Subjects participated in "Neurobiology of Late-life Depression" (NBOLD) study at the University of Connecticut Health Center (UCHC) and Olin Neuropsychiatry Research Center at the Institute of Living in Hartford Hospital. Participants were screened for depression using the Center for Epidemiologic Studies – Depression (CES-D) scale, with a score of 16 or greater as a cut-off for depression. The NEO PI-R was used to screen for neuroticism. CERAD neurophysiological tests were used to screen for cognitive decline, and were administered annually. Statistical analysis of the data involved linear regression and correlation analysis was done to assess the significance of the predictive value of various facets of neuroticism in future cognitive decline development. Mixed model analysis was done to examine how changes in neuroticism score can moderate the rate of cognitive decline. Analysis was done by using baseline neuroticism scores and cognition scores after one, two, and three years. <h3>Results</h3> 163 subjects were enrolled. 28.8% of subjects identified as male, and 71.2% identified as female. The mean age was 72.27 ± 7.44 years. 89.6% identified as White, 7.7% identified as Black or African American, 1.8% identified as Asian, and 0.61% identified as mixed race. 1.8% had completed 9^th grade, 14.1% had graduated high school, 22.7% had completed some college, 20.9% had a college degree, and 40.5% had completed post-graduate education124 subjects had depression at the time of baseline measurement, and 39 comparison subjects did not have depression at baseline. Two facets of neuroticism were shown to be statistically significant predictors of cognitive decline in the non-depressed patients. High baseline N6 (vulnerability of stress) was a predictor of a lower CERAD score at 1 year (p=0.08) and 3 years (p=0.09). High baseline N4 (self-consciousness) was also found to be a predictor of lower CERAD score at 1 year (p=0.01), 2 years (p=0.03), and 3 years (p=0.08). In addition, improvement in N4 over time was shown to cause a lower rate of progression of cognitive decline in non-depressed patients. The findings for depressed patients were not found to be statistically significant. <h3>Conclusions</h3> Both N6 and N4 are statistically significant predictors of cognitive decline 1 to 3 years after baseline neuroticism measurement. Improvement in N4 is associated with a lower rate of cognitive decline. These results were found in non-depressed patients but not depressed patients. These findings raise the possibility that longer periods of follow-up are needed to illustrate the association between neuroticism, cognitive decline, and depression. Investigating predictive factors of cognitive decline is key to foreseeing the development of the disease early on, allowing patients to prepare and access care that may be difficult to obtain as cognitive conditions progress. <h3>This research was funded by</h3> All subjects in the study were enrolled in NBOLD, a NIMH R01 grant entitled "Neurobiology and Adverse Outcomes of Neuroticism in Late-Life Depression".

Evaluating the Effects of the COVID-19 Pandemic on Depression and Resilience in Older Adults

IntroductionSince March 2020, the COVID-19 pandemic has affected the physical and mental health of older adults. We know how social isolation and loneliness may adversely affect one's health, mood, and cognition, specifically in adults over 65. However, when faced with adversity, studies have shown older adults to be at least, if not more, resilient than their younger counterparts. This study aimed to understand the extent of psychosocial impact the pandemic had on older adults with and without depression currently enrolled in the Neurobiology of Late-Life Depression (NBOLD) Study. In conjunction with the Brief Carroll Depression and Brief Resilience Scales, we used a novel measure of pandemic-related experiences across several life domains in older adults, the Epidemic-Pandemic Impacts Inventory-Geriatrics Adaptation (EPII-G).Based on prior knowledge of how detrimental social isolation can be on mental health and how resilient older people can be, we hypothesized that depression scores would increase during the pandemic. We also suspected that resilience scores at least remain constant or possibly improve.According to the Centers for Disease Control and Prevention, adults 65 and older account for 14.3% of cases and 80% of COVID-19 related deaths in the United States. Between “stay at home” guidelines and visitation restrictions along the continuum of aging services, there is concern over the lasting effects of social isolation. Therefore there is a need to examine and map the ways by which one's physical and social environments impact loneliness. Although loneliness is considered to be a subjective feeling related to a person's experience, it is one of three main factors leading to depression and a factor in cause of suicide.Despite this, one characteristic has shown to be protective against these stressors. Resilient individuals exhibit internal qualities like self-reliance and optimism and have external support systems in place allowing them to adapt more readily in the face of change.There is still little research available regarding outcomes and factors from COVID-19 impacting older adults’ depression and resilience, which this study aims to address, while strengthening the validity of the EPII-G.MethodsThe study population included older adults previously diagnosed with Major Depressive Disorder (MDD) and non-depressed controls, enrolled in the N-BOLD study at University of Connecticut Health Center. Inclusion criteria for participants included: age of 60 or greater, ability to read and write English, and Mini-Mental State Examination score of 25 or greater. Depressed subjects met the criteria for MDD, either episodic or recurrent. Participants provided additional informed consent for the study. Baseline data was collected prior to the COVID-19 pandemic, with second interviews taking place mid-2020, and additional follow-up summer 2021. The study utilized the EPII-G, Brief Carroll Depression Scale (BC), and Brief Resilience Scale (BRS). The surveys were verbally administered by the research staff both in-person and via phone interviews.ResultsFrom mid-2020 to summer 2021, both depressed and emotional control groups saw an increase in total BC depression score. Older adults with a history of depression showed BC scores increase from 2.47 to 3.12, and older controls experienced increases from 0.5 to 1.11.Despite an increase in depression score, both cohorts also saw an increase in BRS resilience score, with the depressed group and control group showing increases in BRS from 18.18 to 19.75 and 20.93 to 23.33 respectively.We found a negative correlation between positive home life of person in the home on EPII-G and BC scores, with a correlation coefficient of -0.3645 and p-value of 0.0616. There was also a positive correlation with positive home life of person in the home and social activities for self and BRS scores, with correlation coefficients of 0.26304 and 0.29869 and p-values of 0.0845 and 0.0489 respectively.ConclusionsIndividuals who didn't see disruption to their normal routine and had the means to communicate with loved ones had strong psycho-social supports in place, but were still vulnerable to the detrimental effects of isolation. Through their years of experience, older adults have had the time needed to develop protective factors such as self-reliance. They have also lived through poignant events such as war and economic depression, putting suffering into perspective. As many no longer work or attend school like their younger counterparts, they experienced less disruption to daily routine. This strong foundation has contributed to the resilience needed to overcome the stressors that surfaced during the pandemic.By continuing to follow these groups, we can evaluate changes in depressive symptoms, how long they persist, and if individuals return to baseline over time, as well as to continue to strengthen the EPII-G's validity.This research was funded byResearch is supported by National Institute of Mental Health grant R01 MH108578.Chart: https://apps.aagponline.org/abstracts/uploads/2022/f1peuxbywkablos.pdf

Association of 1-year change in neuroticism and 3-year change in cognitive performance among older depressed adults.

The relationships among depression, personality factors, and cognitive decline in the elderly are complex. Depressed elders score higher in neuroticism than nondepressed older individuals. Presence of neuroticism worsens cognitive decline in depressed older adults. Yet little is known about changes in neuroticism among older adults being treated for depression and the impact of these changes on cognitive decline. Longitudinal observational study. Academic Health Center. We examined 68 participants in the neurobiology of late-life depression (LLD) study to test the hypothesis that older depressed subjects with more improvement in neuroticism would experience less cognitive decline compared with those with less change in neuroticism. We measured neuroticism using the NEO-Personality Inventory-Revised at baseline and 1 year. Study psychiatrists measured depression using the Montgomery-Åsberg depression rating scale (MADRS). Global cognitive performance was measured using the Consortium to Establish a Registry for Alzheimer's disease (CERAD) battery at baseline and annually over 3 years. Regression models of 1-year change in neuroticism and 3-year change in CERAD included sex, age, race, education, and 1-year change in MADRS score as covariates. We found that among older adults, 1-year change in neuroticism was inversely associated with 3-year change in CERAD total score. Our findings challenge the notion of longitudinal stability of measures of personality, especially among older depressed individuals. They highlight the importance of repeated personality assessment, especially of neuroticism, in the management of LLD. Future studies in larger samples followed for longer periods are needed to confirm our results and to extend them to examine both cognitive change and development of dementia.

Positron emission tomography imaging of serotonin degeneration and beta-amyloid deposition in late-life depression evaluated with multi-modal partial least squares

Depression in late-life is associated with increased risk of cognitive decline and development of all-cause dementia. The neurobiology of late-life depression (LLD) may involve both neurochemical and neurodegenerative mechanisms that are common to depression and dementia. Transgenic amyloid mouse models show evidence of early degeneration of monoamine systems. Informed by these preclinical data, the hypotheses were tested that a spatial covariance pattern of higher beta-amyloid (Aβ) and lower serotonin transporter availability (5-HTT) in frontal, temporal, and parietal cortical regions would distinguish LLD patients from healthy controls and the expression of this pattern would be associated with greater depressive symptoms. Twenty un-medicated LLD patients who met DSM-V criteria for major depression and 20 healthy controls underwent PET imaging with radiotracers for Aβ ([11C]-PiB) and 5-HTT ([11C]-DASB). A voxel-based multi-modal partial least squares (mmPLS) algorithm was applied to the parametric PET images to determine the spatial covariance pattern between the two radiotracers. A spatial covariance pattern was identified, including higher Aβ in temporal, parietal and occipital cortices associated with lower 5-HTT in putamen, thalamus, amygdala, hippocampus and raphe nuclei (dorsal, medial and pontine), which distinguished LLD patients from controls. Greater expression of this pattern, reflected in summary 5-HTT/Aβ mmPLS subject scores, was associated with higher levels of depressive symptoms. The mmPLS method is a powerful approach to evaluate the synaptic changes associated with AD pathology. This spatial covariance pattern should be evaluated further to determine whether it represents a biological marker of antidepressant treatment response and/or cognitive decline in LLD patients.

Cognitive variability, brain aging, and cognitive decline in late-life major depression.

Older adults with late-life major depression (LLMD) are at increased risk of dementia. Dispersion, or within-person performance variability across cognitive tests, is a potential marker of cognitive decline. This study examined group differences in dispersion between LLMD and nondepressed healthy controls (HC) and investigated whether dispersion was a predictor of cognitive performance 1 year later in LLMD. We also explored demographic, clinical, and structural imaging correlates of dispersion in LLMD and HC. We hypothesized that dispersion would be greater in LLMD compared with HC and would be associated with worse cognitive performance 1 year later in LLMD. Participants were enrolled in the Neurobiology of Late-Life Depression, a naturalistic longitudinal investigation of the predictors of poor illness course in LLMD. The baseline sample consisted of 121 older adults with LLMD and 39 HC; of these subjects, 94 LLMD and 35 HC underwent magnetic resonance imaging (MRI). One-year cognitive data were available for 107 LLMD patients. All participants underwent detailed clinical and structural MRI at baseline. LLMD participants also completed a comprehensive cognitive evaluation 1 year later. Higher test dispersion was evident in LLMD when compared with nondepressed controls. Greater baseline dispersion predicted 1-year cognitive decline in LLMD patients even when controlling for baseline cognitive functioning and demographic and clinical confounders. Dispersion was correlated with white matter lesions in LLMD but not HC. Dispersion was also correlated with anxiety in both LLMD and HC. Dispersion is a marker of neurocognitive integrity that requires further exploration in LLMD.

Neurotransmitters and Neurometabolites in Late-Life Depression: A Preliminary Magnetic Resonance Spectroscopy Study at 7T

BackgroundMagnetic resonance spectroscopy (MRS) methods have quantified changes in levels of neurotransmitters and neurometabolites in patients with major depression across the lifespan. The application of 7T field strengths and greater have not been a major focus of study in patients with late-life depression (LLD). MethodsNine LLD patients who met DSM-IV criteria for a current major depressive episode and nine non-depressed, healthy, age-matched controls underwent clinical and neuropsychological assessment and single-voxel 7T 1H-MRS at baseline and after 10-12 weeks of antidepressant treatment (Citalopram; patients only). Spectra were acquired from two brain regions implicated in both depressive symptoms and neuropsychological deficits in LLD, the anterior (ACC) and posterior cingulate (PCC). Levels of γ-aminobutyric acid (GABA), glutamate (Glu), glutathione (GSH), N-acetylaspartylglutamate (NAAG), N-acetylaspartate (NAA), and myo-inositol (mI) were quantified relative to total creatine (tCr) using linear-combination modeling. ResultsBaseline Glu/tCr levels were not significantly different between groups. Decreased Glu/tCr levels after Citalopram treatment were observed in a subset of LLD patients. Exploratory analyses showed that LLD patients had lower NAA levels in the PCC relative to controls. Higher levels of ml in the LLD patients relative to the controls and decreases after Citalopram treatment had large effect sizes but were not statistically significant. Further, decreases in PCC Glu/tCr and increases in ACC GSH/tCr were associated with improvement in depressive symptoms. LimitationsSample size. ConclusionsThese preliminary results suggest a role of neurochemicals and neurometabolites in the neurobiology of LLD and antidepressant treatment response.

PRESENCE OF OPTIMISM AND ANTIDEPRESSANT REMISSION RATES IN LATE-LIFE DEPRESSION

Introduction Interest in personality traits and their relationship to depression has grown in recent years. The Big Five model of personality is often used as the standard framework in which personality constructs can be better understood. The model includes: (1) Extraversion/Positive Emotionality, (2) Agreeableness, (3) Conscientiousness, (4) Emotional Stability versus Neuroticism, and (5) Openness/Intellect. However, there is growing interest in optimism since it has been linked to low Neuroticism and high Extraversion/Positive Emotionality (Sharpe et al 2011). Optimism, defined as the extent to which people hold generalized favorable expectancies for their future, is also inversely related to hopelessness, a risk factor for depressive disorders. Prior research suggests that optimists tend to have high Emotional Stability, Extraversion, Agreeableness, and Conscientiousness, resulting in a tendency toward better mental and physical health, adaptive behavior, and even lower mortality rates (Achat et al 2000 and Armbruster et al 2015). Optimism remains understudied in older adults, particularly as most of the prior research has explored optimism as a construct of Neuroticism and Extraversion in younger and middle-aged adults (Armbruster et al 2015). We aimed to examine the effects of optimism on acute treatment outcome in a group of older depressed adults initially treated with the antidepressant sertraline in an open-label fashion as part of Neurobiology of Late-Life Depression (NBOLD), a US National Institute of Mental Health (NIMH)- supported study at the University of Connecticut (UConn). We hypothesized that presence of high optimism would be associated with lower 12-week remission rates in older depressed sertraline-treated patients. Methods In this longitudinal cohort study, all subjects were enrolled in NBOLD and recruited from clinic referrals and newspaper advertisements. Inclusion criteria for depressed subjects were age 60 or above, ability to read and write English, Mini- Mental State Examination (MMSE) score 25 or greater and meeting criteria for major depression, single episode, or recurrent (DSM-IV-TR). A total of 74 subjects were included and were administered the Montgomery–Ǻsberg Depression Rating Scale (MADRS) and Cumulative Illness Rating Scale (CIRS), as modified for geriatric patients. Each subject completed several self-report measures, including the Life Orientation Test- Revised (LOT-R, Scheier et al 1994), which measures total optimism. We used regression analyses to examine factors related to 12-week remission of depression (MADRS score Results We found that higher total optimism was not associated with lower likelihood of remission among both the intention-to-treat group and sertraline completers after controlling for baseline MADRS and CIRS score. Additional regression analyses of optimism, neuroticism and apathy were also examined, but were not associated with lower likelihood of remission. Conclusions Our results do not support that optimism alone can predict depression outcomes in older adults. Although optimism has been shown to have predictive value in younger and middle-aged adults, there may be other medical comorbidities such as somatic illness, as well as increasing psychosocial stressors, contributing to the development of late life depression that override the effects of optimism. This may explain why optimism, although important in older age, may not have strong predictive accuracy for health-related outcomes. Our findings are consistent with a prior study examining optimism and depression outcomes in younger vs older adults in which predictive accuracy decreases with age (Armbruster et al 2015). This research was funded by: Neurobiology of Late-Life Depression (NBOLD), a US National Institute of Mental Health (NIMH)- supported study at the University of Connecticut (UConn)

PERSONALITY DIFFERENCES IN LATE-LIFE DEPRESSION AND MILD COGNITIVE IMPAIRMENT

Introduction Previous research has shown links between depression, personality factors, and cognitive decline. For example, Alzheimer's patients show higher levels of neuroticism and lower levels of openness, agreeableness, conscientiousness, and extraversion as compared to cognitively normal older adults as stated in a meta-analysis conducted by D'lorio et al. (2018). Elsewhere, one study found older adults who transitioned from cognitively normal aging to mild cognitive impairment experienced an increase in neuroticism and depression as well as a decrease in openness (Caselli et al., 2018). The current study examined personality differences between older adults with major depression and non-depressed cognitively normal controls and depressed patients with and without mild cognitive impairment. Based off of prior work using a different sample, we hypothesized higher levels of neuroticism and lower levels of openness, conscientiousness, agreeableness, and extraversion between patients and controls. We further hypothesized that patients with memory impairment (amnestic MCI) would exhibit decreased conscientiousness, openness, extraversion, and agreeableness and increased neuroticism compared to patients without memory impairment, a pattern of performance similar to AD patients. Methods Data from the Neurobiology of Late-Life Depression (NBOLD) study were used. Individuals were either depressed patients or never-depressed controls. We further divided patients and controls into cognitively normal or mild cognitive impairment groups using psychometric criteria from Bondi and Jak (ref). Personality, depression, and cognition were assessed using the NEO Personality Inventory (NEO-PI), Montgomery-Asberg Depression Rating Scale (MADRS), and the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) cognitive battery, respectively. A t-test for independent samples and a general linear modeling via MANOVA with covariates were conducted to examine group differences between patients and controls as well as between patients with amnestic MCI and without amnestic MCI. Results Patients (N=117) showed higher levels of neuroticism (F=90.33, p= Conclusions There are statistically significant personality differences in neuroticism, extraversion, and conscientiousness between patients and controls, indicating an interaction between depression and personality factors. Older adults with depression and memory impairment reported less sociability and less openness to new experiences compared to older adults with depression and no memory impairment. Future studies should examine whether early changes in personality are a marker of cognitive decline in older adults with major depression. This research was funded by: This research was supported by The Leo and Anne Albert Charitable Trust and NIMH Grant R01 MH108578. The authors would like to acknowledge the support of the Department of Health Career Opportunity Programs, Aetna Health Professions Partnership Initiative.

MEMORY COMPLAINTS AND DEPRESSION TREATMENT IN OLDER ADULTS

Introduction Older adults with major depression (or late-life depression) often complain about problems with thinking and memory. Some evidence suggests that subjective cognitive complaints may be a useful prognostic indicator of response to antidepressant medication. In one prior study, older adults with major depression and executive functioning complaints responded more slowly to escitalopram treatment over 12 weeks compared with older depressed adults with no executive functioning complaints. It is unclear whether the potential association between subjective cognitive complaints and treatment response generalizes to other cognitive domains and whether there is a longer-term relationship between treatment response and subjective cognitive complaints. The aim of the current study is to understand the relationship between subjective memory complaints and late-life depression treatment response at 12 weeks and one-year. The mechanism explaining the potential association between subjective cognitive complaints and treatment responses is unclear. Subjective memory complaints may represent subtle changes in objective memory test performance. Better objective story memory at baseline was associated with better depression outcomes one-year later in older adults with major depression. However, a large body of research also suggests subjective memory complaints in older adults are related to the severity of depression, anxiety, and/or personality traits (e.g., neuroticism), all factors that detrimentally influence depression treatment in older adults. Given these findings, we expected to find an association between subjective memory complaints and treatment response in late-life depression but hypothesized that the association would no longer be significant when controlling for depression severity, state anxiety, neuroticism, and objective memory performance. Methods The Neurobiology of Late-Life Depression (NBOLD) is a naturalistic longitudinal observation study of late-life depression. Upon enrollment, all patients were offered open label treatment with sertraline but this was not a requirement of participation. Instead, patients could have received other SSRIs/SNRIs and psychological treatment from non-study providers. Moreover, in some cases of mild major depression, patients may have elected not to receive treatment at all. All subjects underwent annual cognitive evaluations and depression monitoring with the Montgomery Asberg Depression Rating Scale (MADRS) as clinically indicated (and at least every three months). At baseline, subjective memory complaints were measured with the Memory Abilities Scale (MAB), state anxiety was measured with State-Trait Anxiety Inventory (STAI), and neuroticism was measured with the NEO-PI-R. Statistical Analyses: We conducted regression models testing the association between 12 week and one-year MADRS and baseline subjective memory complaints, objective memory performance (Logical Memory Delayed Recall), state anxiety, neuroticism, antidepressant usage, and relevant demographics. We tested both linear (continuous MADRS score) and logistic (yes-no presence of remission defined as MADRS Results The sample consisted of 90 patients at 12 weeks and 85 at one year. Regarding antidepressant treatment, 47.5% of LLD patients (n=57) began treatment with sertraline upon enrollment, 27.5% (n=33) were on some other SSRI and/or SNRI combination, and 25% were not receiving antidepressants. Contrary to our hypotheses, linear regression models revealed that baseline subjective memory complaints were a significant predictor of 12 week (Coefficient = -.087 +- .038, p = .025) and one-year MADRS (Coefficient = -.097 +- .039, p = .014) scores even when accounting for objective memory performance (Logical Memory Delayed Recall), state anxiety, neuroticism, antidepressant usage, and relevant demographics. Using the same covariates, subjective memory complaints also predicted remission at 12 weeks (OR[95%CI] = 1.07 (1.02, 1.11) p Conclusions Subjective memory complaints seem to be a useful indicator of depression treatment response in older adults with major depression. Notably the relationship between subjective memory complaints and treatment response was present even when accounting for other important factors shown to be related to subjective cognitive complaints and treatment outcome. Future work should investigate the biological and cognitive correlates of subjective memory complaints in older adults with major depression. This research was funded by: The research was supported by the Leo and Anne Albert Charitable Trust & NIMH Grant R01 MH108578.

PATIENT VERSUS CLINICIAN RATED DEPRESSION SCORES: A COMPARISON OF PARTICIPANT SCORES ON THE CARROLL DEPRESSION SCALE AND THE HAMILTON DEPRESSION RATING SCALE

Introduction In clinical practice, physicians and other medical providers rely heavily on self-assessment tools to screen and assess severity of psychiatric illness, including depression. Ensuring that these self-rating depression scales correlate to investigator rated depression scales is important for diagnosis, validity, and patient care. Several studies have demonstrated a strong correlation between adult patient rated scales compared to clinician completed depression scales which served to establish the validity of self-reported tests. To the best of our knowledge, no studies have been performed in depressed older adults to compare the correlation of self-report versus clinician completed depression scales. We hypothesized that older adults would rate depression higher on self-reported scales compared to clinician completed depression scales and that variables such as cognition would contribute to these findings. Methods Using data collected from the Neurobiology of Late Life Depression (NBOLD) study, we compared the 61-item self-report Carroll Depression Scale – Revised (CDS-R) scores against the 17-item clinician rated Hamilton Depression Rating Scale (HAM-D) scores in 100 depressed patients that were obtained on the same day as part of the study baseline assessment battery. Based on the crosswalk between CDS-R and HAM-D, the first 52 questions from the CDS-R were compared with the HAM-D. Spearman correlation, weighted kappa coefficient (κ), scatter plot, and linear regression were used to determine the agreement between CDS-R scores and HAM-D scores, and evaluate potential influencing factors for any discrepancy. Both total score and the 17 individual domain-specific subscale scores were examined. Results Consistent with the hypothesis, CDS-R total score (mean 19.6, SD 6.8) were found to be, on average, six points higher than HAM-D total score (mean 13.4, SD 3.9). This six point difference between CDS-R and HAM-D was consistent along the range of depression severity, as demonstrated in figure 1. Comparing domains within each assessment tool, suicidal tendency, weight loss, early insomnia had the highest correlation, while agitation, insight, and general somatic symptoms had lower correlations. The relationship between CDS-R total score and HAM-D total score was not affected by age, gender, Montgomery and Ǻsberg Depression Rating Scale (MADRS), and Cumulative Illness Rating Scale (CIRS) total scores. Cognition, as indicated by CERAD total score, was the only statistically significant covariate for predicting CDS-R total score in a model that included HAM-D score, which supported the hypothesis. Conclusions Self-assessment screening tools, including those for depression, are important tools for researchers and clinicians alike. These screening tools, such as the Carroll Depression Scale, have demonstrated positive correlation compared with clinician completed scales, such as the Hamilton Depression Rating Scale. Similarly, this data analysis demonstrated positive correlation between the CDS-R and HAM-D in older adults. Limitations of this study include small sample size and mild to moderate depression scores in this ambulatory population. Additional studies would be beneficial to compare other depression rating scales, especially in older adults. Other research is needed to investigate variables that may attribute to higher rates of self-reported depression symptoms. This research was funded by Not Applicable

Presence of neuroticism and antidepressant remission rates in late-life depression: results from the Neurobiology of Late-Life Depression (NBOLD) study.

ABSTRACTNeuroticism in older adults is common yet understudied, particularly its effects on depression treatment outcomes. We hypothesized that presence of high neuroticism would be associated with lower 12-week remission rates in older depressed sertraline-treated patients. In this longitudinal cohort study, 43 depressed older adults completed the Revised NEO Personality Inventory (NEO PI-R). A study psychiatrist administered the Montgomery Ǻsberg Depression Rating Scale (MADRS), and the Cumulative Illness Rating Scale (CIRS, a measure of medical burden) at baseline, and the MADRS at each clinical visit. All subjects began open-label sertraline treatment and were followed over 12 weeks with clinically indicated flexible dosing and an option to switch antidepressants. We used regression analyses to examine factors related to 12-week remission of depression (MADRS score < 8) and final MADRS score. We found that higher total neuroticism (odds ratio (OR) = 0.963, 95% confidence interval (CI) = 0.928-1.000) and a neuroticism subscale, stress vulnerability (OR = 0.846, 95% CI = 0.728-0.983), were associated with lower likelihood of remission among both the intention-to-treat group and sertraline completers. Findings remained significant after controlling for baseline MADRS and CIRS score. In conclusion, assessment of personality, particularly features of neuroticism, may be important in management of late-life depression. Future studies should determine if depressed patients high in neuroticism may benefit from psychotherapy focusing on emotional regulation and stress management.

Negative Affectivity, Aging, and Depression: Results From the Neurobiology of Late-Life Depression (NBOLD) Study

Neuroticism is a common yet understudied condition in older adults. We hypothesized that presence of high negativity affectivity (NA), a key feature of neuroticism, would be associated with different prefrontal cortex (PFC) activity and connectivity patterns in depressed and never-depressed older adults. This is a baseline cross-sectional analysis of a cohort study of 52 depressed and 36 never-depressed older adults. Assessments included NA scores from the Type D Scale-14 and Montgomery-Åsberg Depression Rating Scale scores. All subjects had a 3T brain functional magnetic resonance imaging resting scan, neuronal activity determined by amplitude of low-frequency fluctuations (ALFFs) were obtained, and resting state functional connectivity (FC) analyses were performed. Analyses of covariance were conducted on ALFFs and FC to examine significant differences between groups. In the ALFF analyses there were clearly different patterns between depressed and comparison groups in the correlation of ALFFs and NA. The correlation differences between the two groups were significant in the dorsomedial PFC, insula, amygdala, and posterior cingulate cortex (PCC). FC analyses revealed different between-group connectivity patterns. Significantly higher ventromedial PFC-amygdala FC with NA correlation was found in the depressed group than that in the never-depressed group. This study confirms differential activity of the dorsal and ventral regions of the medial PFC in individuals with high neuroticism. Our findings suggest increased rostral medial PFC activity may be a marker of resilience to depression in the elderly and decreased anterior ventromedial PFC, PCC, and amygdala activity may be a result of successful emotion regulation in never-depressed higher NA individuals.

The neurobiology of late-life depression: Impact of silent cerebrovascular disease

Depression in the elderly is associated with increased mortality, persistence of symptoms and progression to dementia in a substantial number of cases. Minor cerebrovascular lesions such as deep white matter changes, lacunar infarcts and silent cerebral infarction can be demonstrated in some late-onset depressives and may be relevant to the development of depression, or associated with the persistence of symptoms and the emergence of treatment resistance. Increased morbidity and mortality may occur through subsequent cerebrovascular events, and progression to dementia might result from multiple cerebral infarcts. Treatment strategies that address underlying vascular risk factors could decrease the likelihood of fatal strokes or stepwise progression to (multi-infarct) dementia, thereby improving the long-term prognosis for a subgroup of late-onset depressives.