Recent research has linked age-related hearing loss to impaired performance across cognitive domains and increased risk for dementia diagnosis. The data linking hearing impairment to incident late-life depression are more mixed but suggest that diminished hearing does increase risk for depression. Behavioral mechanisms may explain these associations, such as the withdrawal of older adults from situations in which they may have difficulty hearing and communicating, which may contribute to the development of social isolation, loneliness, and consequent cognitive decline and depression. At a neural level, chronic hearing loss leads to reduced activation in central auditory pathways, resulting in compensatory increased activation in the cognitive control network, dysfunctional auditory–limbic connectivity, and deafferentation-induced atrophy in frontal brain regions. These pathologic changes decrease cognitive performance and increase depression risk by reducing cognitive reserve, increasing executive dysfunction, and disrupting normative emotion reactivity and regulation. Based on the available data and informed by this model, evidence-based suggestions are proposed for clinicians treating older adults, and a research agenda is advanced to facilitate the development of rationally designed and age-appropriate psychiatric treatments for older adults with age-related hearing loss. First and foremost, treating hearing loss should be investigated as a means of improving cognitive and depressive outcomes in well-designed studies incorporating comprehensive psychiatric assessments, randomization, objective documentation of compliance, and analyses of treatment mediators that will facilitate further therapeutic development. Multimodal neuroimaging studies integrating audiometric, neuropsychological, and clinical assessments also are needed to further evaluate the model proposed.

Placebo response in clinical trials of antidepressant medications is substantial and increasing. High placebo response rates hamper efforts to detect signals of efficacy for new antidepressant medications, contributing to more failed trials and delaying the delivery of new treatments to market. Media reports seize upon increasing placebo response and modest advantages for active drugs as reasons to question the value of antidepressant medication, which may further stigmatize treatments for depression and dissuade patients from accessing mental health care. Conversely, enhancing the factors responsible for placebo response may represent a strategy for improving available treatments for Major Depressive Disorder. A conceptual framework describing the causes of placebo response is needed in order to develop strategies for minimizing placebo response in clinical trials, maximizing placebo response in clinical practice, and talking with depressed patients about the risks and benefits of antidepressant medications. This review examines contributors to placebo response in antidepressant clinical trials and proposes an explanatory model. Research aimed at reducing placebo response should focus on limiting patient expectancy and the intensity of therapeutic contact in antidepressant clinical trials, while the optimal strategy in clinical practice may be to combine active medication with a presentation and level of therapeutic contact that enhances treatment response.

Objectives To identify salient characteristics of frailty that increase risk of death in depressed elders. Design Data from the Nordic Research on Ageing Study. Setting Research sites in Denmark, Sweden, and Finland. Participants Sample included 1027 75-year-old adults, 436 men and 591 women. Main Outcome Measure Time of death was obtained, providing a maximum survival time of 11.08 years (initial evaluation took place between 1988-1991). Results Depressed elders showed greater baseline impairments in each frailty characteristic (gait speed, grip strength, physical activity levels, and fatigue). Simultaneous models including all four frailty characteristics showed slow gait speed (HR, 1.84; 95% CI, 1.05-3.21) and fatigue (HR, 1.94; 95% CI, 1.11-3.40) associated with faster progression to death in depressed women; none of the frailty characteristics in the simultaneous model were associated with death in depressed men. In women, the effect of impaired gait speed on mortality rates nearly doubled when depression was present (mortality rates, nondepressed women: no gait impairment =26%; slow gait =40%; depressed women: no gait impairment=32%; slow gait =58%). A similar pattern was observed for fatigue. Conclusions The confluence of specific characteristics of frailty (fatigue and slow gait speed) and depressive illness is associated with an increased risk of death in older adults; this association is particularly strong in older depressed women. Future research should investigate whether multimodal interventions targeting depressive illness, mobility deficits, and fatigue can decrease mortality and improve quality of life in older depressed individuals with characteristics of the syndrome of frailty.

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Objective Causes of placebo effects in antidepressant trials have been inferred from observational studies and meta-analyses, but their mechanisms have not been directly established. The goal of this study was to examine in a prospective, randomized controlled trial (RCT) whether patient expectancy mediates placebo effects in antidepressant studies. Method Adult outpatients with Major Depressive Disorder (MDD) were randomized to Open or Placebo-controlled citalopram treatment. Following measurement of pre- and post-randomization expectancy, subjects were treated with citalopram or placebo for 8 weeks. Independent samples t tests determined whether patient expectancy differed between the Open and Placebo-controlled Groups, and mixed-effects models assessed Group effects on Hamilton Rating Scale for Depression (HRSD) scores over time while controlling for treatment assignment. Finally, mediation analyses tested whether between-Group differences in patient expectancy mediated the Group effect on HRSD scores. Results Post-randomization expectancy scores were significantly higher in the Open Group (12.1 ± 2.1) as compared to the Placebo-controlled Group (11.0 ± 2.0, t=2.32, df 45, p=0.03). Mixed-effects modeling revealed a significant Week × Group interaction (F(1,296)=8.61, p=0.0036), indicating that HRSD scores for citalopram-treated subjects declined at a faster rate in the Open Group compared to the Placebo-controlled Group. Patient expectations post-randomization partially mediated Group effects on Week 8 HRSD (p=0.046). Conclusions Patient expectancy is a significant mediator of placebo effects in antidepressant trials. Expectancy-related interventions should be investigated as a means of controlling placebo responses in antidepressant clinical trials and improving patient outcome in clinical treatment.

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Depression in later life is a severe public health problem, associated with higher rates of mortality, suicide, and dementia. Effectiveness of treatment is limited by the failure to deconstruct the heterogeneity of the illness and because diagnostic criteria, pathophysiological models, and treatment algorithms for depression are primarily based on studies of younger adults even though symptoms of the illness and physiology of the patient change with age. Thus, understanding how aging interacts with depressive illness may elucidate endophenotypes of late life depression with different clinical manifestations and underlying mechanisms that can then be targeted with more personalized approaches to treatment. This paper proposes a model for the critical confluence between depression and frailty, a high-risk morbidity and mortality syndrome of later life. This model hypothesizes that characteristics of frailty in adults with late life depression represent the clinical manifestation of greater biological aging and their presence in the context of a depressive illness exposes elders to deleterious trajectories. Potential common biological substrates that may result in the manifestation of the depressed frail phenotype including mitochondrial functioning, dopaminergic neurotransmission, and inflammatory processes and implications for the assessment and treatment of adults with late life depression are discussed. As society continues to live longer, the preservation of the quality of these added years becomes paramount, and the combined impact of depression and frailty on the preservation of this quality warrants the attention of clinical researchers and physicians.

Button-pressing generates smaller P300 than silent-counting. Also, P300 topography in button-pressing tasks is confounded by motor potentials. The distortion can be corrected with a motor potential estimate. Motor potentials can occlude differences in P300 topography between groups.