Enhanced Molecular Aging in Late-Life Depression: the Senescent-Associated Secretory Phenotype.

Objective: This study aims to investigate whether a systemic molecular pattern associated with aging (senescent-associated secretory phenotype [SASP]) is elevated in adults with late-life depression (LLD), compared with never-depressed elderly comparison participants.

Design: Cross-sectional study.

Participants: We included 111 older adults (80 with LLD and 31 comparison participants) in this study.

Circulating biosignatures of late-life depression (LLD): Towards a comprehensive, data-driven approach to understanding LLD pathophysiology.

There is scarce information about the pathophysiological processes underlying Late-Life Depression (LLD). We aimed to determine the neurobiological abnormalities related to LLD through a multi-modal biomarker approach combining a large, unbiased peripheral proteomic panel and structural brain imaging. We examined data from 44 LLD and 31 control participants.

Combining moderators to identify clinical profiles of patients who will, and will not, benefit from aripiprazole augmentation for treatment resistant late-life major depressive disorder.

Personalizing treatment for late-life depression requires identifying and integrating information from multiple factors that influence treatment efficacy (moderators). We performed exploratory moderator analyses using data from a multi-site, randomized, placebo-controlled, double-blind trial of aripiprazole augmentation. Patients (n = 159) aged ≥60 years had major depressive disorder that failed to remit with venlafaxine monotherapy.

Immunological biomarkers associated with brain structure and executive function in late-life depression: exploratory pilot study.

Objective: Several immunological biomarkers are altered in late-life major depressive disorder (LLD). Immunological alterations could contribute to LLD's consequences, but little is known about the relations between specific immunological biomarkers and brain health in LLD. We performed an exploratory pilot study to identify, from several candidates, the specific immunological biomarkers related to important aspects of brain health that are altered in LLD (brain structure and executive function).

Predictors and Moderators of Remission With Aripiprazole Augmentation in Treatment-Resistant Late-Life Depression: An Analysis of the IRL-GRey Randomized Clinical Trial.

Importance: Safe, efficacious, second-line pharmacological treatment options exist for the large portion of older adults with major depressive disorder who do not respond to first-line pharmacotherapy. However, limited evidence exists to aid clinical decision making regarding which patients will benefit from which second-line treatments.

Objective: To test the moderating role of pretreatment executive function, severity of anxiety, and severity of medical comorbidity in remission of treatment-resistant late-life depression after aripiprazole augmentation.

Inflammatory markers among adolescents and young adults with bipolar spectrum disorders.

Objective: Despite burgeoning literature in middle-aged adults, little is known regarding proinflammatory markers (PIMs) among adolescents and young adults with bipolar disorder. Similarly, few prior studies have considered potential confounds when examining the association between PIMs and bipolar disorder characteristics. We therefore retrospectively examined these topics in the Course and Outcome of Bipolar Youth (COBY) study.

Polyunsaturated fatty acids moderate the effect of poor sleep on depression risk.

Although potentially modifiable risk factors for interferon-alpha (IFN-α)-associated depression (IFN-MDD) have been identified, it is not currently known how they interact to confer risk. In the present study we prospectively investigated interactions among poor sleep quality, high-stress, pre-existing depressive symptoms, and polyunsaturated fatty acid status. Non-depressed hepatitis C patients (n=104) were followed prospectively during IFN-α therapy.

Association of Baseline Sleep Quality With Trajectories of Depressive Symptoms in Patients Undergoing Interferon Treatment.

Objective: Some patients with hepatitis C starting interferon-α (IFN-α) therapy experience depression, although many patients do not develop depressive symptoms. We have found that poor sleep is associated with increased depressive symptoms on average. It is unknown whether this association holds generally or is driven by a specific, distinct subgroup.

Antidepressant Response Trajectories and Associated Clinical Prognostic Factors Among Older Adults.

Importance: More than 50% of older adults with late-life major depressive disorder fail to respond to initial treatment with first-line pharmacological therapy.

Objectives: To assess typical patterns of response to an open-label trial of extended-release venlafaxine hydrochloride (venlafaxine XR) for late-life depression and to evaluate which clinical factors are associated with the identified longitudinal response patterns.

Design, Setting, And Participants: Group-based trajectory modeling was applied to data from a 12-week open-label pharmacological trial conducted in specialty care as part of the Incomplete Response in Late Life: Getting to Remission Study.

Effect of 2 psychotherapies on depression and disease activity in pediatric Crohn's disease.

Background: Crohn's disease (CD) is associated with depression. It is unclear if psychosocial interventions offer benefit for depressive symptoms during active CD. In this secondary analysis of a larger study of treating depression in pediatric inflammatory bowel disease, we assessed whether cognitive behavioral therapy (CBT) would differentiate from supportive nondirective therapy in treating depression and disease activity in youth with CD.

Inflammation, psychiatric symptoms, and opioid use are associated with pain and disability in patients with cirrhosis.

Background & Aims: Cirrhosis is associated with significant pain and disability, the etiologies of which are poorly understood. We investigated whether the pain and disability in patients with cirrhosis are associated with systemic inflammation and psychiatric symptoms.

Methods: In a prospective study, we recruited 193 patients with cirrhosis caused by hepatitis C virus infection, nonalcoholic steatohepatitis, or alcohol from the hepatology clinic at the University of Pittsburgh.

Decreased delta sleep ratio and elevated alpha power predict vulnerability to depression during interferon-alpha treatment.

Objective: Although poor sleep accompanies depression, it is unknown which specific sleep abnormalities precede depression. This is similarly the case for depression developing during interferon-α (IFN-α) therapy. Because vulnerability becomes evident in those who slept poorly before IFN-α, we prospectively determined which specific aspect of sleep could predict subsequent depression.

Fibromyalgia symptoms and cirrhosis.

Background: An association between fibromyalgia and hepatitis C virus (HCV) has been previously described. However, the relationship between nonalcoholic steatohepatitis (NASH) and fibromyalgia symptoms has not been assessed, though they share several risk factors.

Aim: We aimed to assess the factors associated with fibromyalgia symptoms across etiologies of liver disease.

Inflammatory cytokine-associated depression.

Inflammatory cytokines can sometimes trigger depression in humans, are often associated with depression, and can elicit some behaviors in animals that are homologous to major depression. Moreover, these cytokines can affect monoaminergic and glutamatergic systems, supporting an overlapping pathoetiology with major depression. This suggests that there could be a specific major depression subtype, inflammatory cytokine-associated depression (ICAD), which may require different therapeutic approaches.

Brain-derived neurotrophic factor levels in late-life depression and comorbid mild cognitive impairment: a longitudinal study.

Changes in brain-derived neurotrophic factor (BDNF) level are implicated in the pathophysiology of cognitive decline in depression and neurodegenerative disorders in older adults. We aimed to evaluate the longitudinal association over two years between BDNF and persistent cognitive decline in individuals with remitted late-life depression and Mild Cognitive Impairment (LLD + MCI) compared to either individuals with remitted LLD and no cognitive decline (LLD + NCD) or never-depressed, cognitively normal, elderly control participants. We additionally evaluated the effect of double-blind, placebo-controlled donepezil treatment on BDNF levels in all of the remitted LLD participants (across the levels of cognitive function).

The relationship between interleukin-1 receptor antagonist and cognitive function in older adults with bipolar disorder.

Objective: Cognitive impairments are a feature of bipolar disorder (BD) and could be worsened by inflammatory cytokines. We determined whether (i) serum interleukin-1 receptor antagonist (IL-1RA) was increased in elderly BD subjects; (ii) whether IL-1RA was associated with worse neurocognitive function; and (iii) whether IL-1RA was associated with white matter integrity.

Methods: Twenty-one euthymic BD patients (65 +/- 9 years) with serum available for IL-1RA measures by enzyme-linked immunoassays were compared with 26 similarly aged control participants.

Anger induced by interferon-alpha is moderated by ratio of arachidonic acid to omega-3 fatty acids.

Objective: Anger worsens in some patients during interferon-alpha (IFN-α) therapy. Elevated anger has also been associated with lower long-chain omega-3 (LCn-3) fatty acid levels. We examined whether fatty acids could influence vulnerability to anger during IFN-α exposure.

Common selective serotonin reuptake inhibitor side effects in older adults associated with genetic polymorphisms in the serotonin transporter and receptors: data from a randomized controlled trial.

Objective: Antidepressant side effects are a significant public health issue, associated with poor adherence, premature treatment discontinuation, and, rarely, significant harm. Older adults assume the largest and most serious burden of medication side effects. We investigated the association between antidepressant side effects and genetic variation in the serotonin system in anxious, older adults participating in a randomized, placebo-controlled trial of the selective serotonin reuptake inhibitor (SSRI) escitalopram.

Brain-derived neurotrophic factor serum levels and genotype: association with depression during interferon-α treatment.

Depression has been associated with inflammation, and inflammation may both influence and interact with growth factors such as brain-derived neurotrophic factor (BDNF). Both the functional Val66Met BDNF polymorphism (rs6265) and BDNF levels have been associated with depression. It is thus plausible that decreased BDNF could mediate and/or moderate cytokine-induced depression.

Depression in Late-Life: a Focus on Prevention.

Depression is a leading cause of disease burden, disability and distress for millions of older adults. Thus, prevention of late-life depression is a priority research area. This article addresses the science of late-life depression prevention with the following: 1) an introduction to the Institute of Medicine framework of universal, selective and indicated prevention as it pertains to late-life depression, with particular attention to successes of indicated and selective prevention in primary care; 2) a discussion of how biomarkers can be integrated into prevention research, using interferon-alpha-induced depression as a model; 3) an outline for expansion of prevention to non-specialist care delivery systems in Low and Middle Income Countries - thus, extending the reach of current successful approaches; 4) a description of a novel approach to simultaneous testing of universal, selective and indicated prevention in late-life depression, with emphasis on study design features required to achieve practical, scalable tests of health impact.

Elevated immune-inflammatory signaling in mood disorders: a new therapeutic target?

Converging translational evidence has implicated elevated immune-inflammatory signaling activity in the pathoetiology of mood disorders, including major depressive disorder and bipolar disorder. This is supported in part by cross-sectional evidence for increased levels of proinflammatory eicosanoids, cytokines and acute-phase proteins during mood episodes, and prospective longitudinal evidence for the emergence of mood symptoms in response to chronic immune-inflammatory activation. In addition, mood-stabilizer and atypical antipsychotic medications downregulate initial components of the immune-inflammatory signaling pathway, and adjunctive treatment with anti-inflammatory agents augment the therapeutic efficacy of antidepressant, mood stabilizer and atypical antipsychotic medications.

Elevated ratio of arachidonic acid to long-chain omega-3 fatty acids predicts depression development following interferon-alpha treatment: relationship with interleukin-6.

Cross-sectional studies have found that an elevated ratio of arachidonic acid to omega-3 fatty acid is associated with depression, and controlled intervention studies have found that decreasing this ratio through administration of omega-3 fatty acids can alleviate depressive symptoms. Additionally, arachidonic acid and omega-3 fatty acids have opposing effects on inflammatory signaling. Exogenous administration of the inflammatory cytokine interferon-alpha (IFN-α) can trigger a depressive episode in a subset of vulnerable people, though associated risk factors remain poorly understood.