Effect of aprepitant on kynurenine to tryptophan ratio in cART treated and cART naïve adults living with HIV.

Changes in tryptophan metabolism affect human physiology including the immune system, mood, and sleep and are associated with human immunodeficiency virus (HIV) pathogenesis. This study investigates whether the treatment of HIV-infected individuals with the neurokinin-1 receptor antagonist, aprepitant, alters tryptophan metabolism.This study utilized archival samples from 3 phase 1B clinical trials "Anti-HIV Neuroimmunomodulatory Therapy with Neurokinin-1 Antagonist Aprepitant"-2 double-blinded, placebo-controlled, and 1 open-label study.

HIV Infection and Depression Among Opiate Users in a US Epicenter of the Opioid Epidemic.

Using a mobile research facility, we enrolled 141 opioid users from a neighborhood of Philadelphia, an urban epicenter of the opioid epidemic. Nearly all (95.6%) met DSM-5 criteria for severe opioid use disorder.

Antiinflammatory effects of aprepitant coadministration with cART regimen containing ritonavir in HIV-infected adults.

Background: HIV-infected individuals, even well controlled with combined antiretroviral therapy (cART), have systemic inflammation and comorbidities. Substance P (SP) is an undecapeptide, which mediates neurotransmission and inflammation through its cognate neurokinin 1 receptor (NK1R). Plasma SP levels are elevated in HIV-infected individuals.

HIV Prevalence Among Hospitalized Patients at the Main Psychiatric Referral Hospital in Botswana.

We examined HIV prevalence among patients 18-49 year olds admitted to a psychiatric hospital in Botswana in 2011 and 2012. The retrospective study analyzed females (F) and males (M) separately, comparing proportions with Chi square test and continuous variables with Wilcoxon rank-sum test, assessing significance at the 5% level. HIV seroprevalence among hospitalized psychiatric patients was much more common among females (53%) compared with males (19%) (p < 0.

Pharmacologic rationale for the NK1R antagonist, aprepitant as adjunctive therapy in HIV.

Background: Many HIV infected individuals with suppressed viral loads experience chronic immune activation frequently developing neurological impairment designated as HIV associated neurocognitive disorder (HAND). Adjunctive therapies may reduce HIV associated inflammation and therefore decrease the occurrence of HAND.

Methods: We have conducted in vitro, animal and clinical studies of the neurokinin 1 receptor (NK1R) antagonist aprepitant in HIV/SIV infection.

The Selective Serotonin Reuptake Inhibitor Citalopram Decreases Human Immunodeficiency Virus Receptor and Coreceptor Expression in Immune Cells.

Background: This study investigated whether the selective serotonin reuptake inhibitor (SSRI) citalopram downregulates the expression of the human immunodeficiency virus (HIV) receptor cluster of differentiation 4 (CD4) and coreceptors chemokine receptor type 5 and chemokine-related receptor type 4 (CCR5 and CXCR4) on peripheral blood mononuclear cells (PBMCs) and macrophages ex vivo as a potential mechanism of reducing susceptibility to HIV infection.

Methods: The sample included 150 participants 18-58 years old (59% women, 65% African American, 61% with depression). Monocyte-depleted PBMCs were treated with phytohemagglutinin for 72 hours and then cultured in the presence of interleukin-2 with vehicle control or the SSRI (10(-6) mol/L) for 2 hours.

Reduction of soluble CD163, substance P, programmed death 1 and inflammatory markers: phase 1B trial of aprepitant in HIV-1-infected adults.

Objective: We evaluated safety, antiviral, immunomodulatory and anti-inflammatory properties of aprepitant - a neurokinin 1 receptor antagonist.

Design: Phase IB randomized, placebo-controlled, double-blinded study.

Methods: Eighteen patients were randomized (nine to aprepitant and nine to placebo).

Influences of hormone replacement therapy on olfactory and cognitive function in postmenopausal women.

Olfactory dysfunction can be an early sign of Alzheimer's disease. Since hormone replacement therapy (HRT) may protect against Alzheimer's disease in postmenopausal women, the question arises as to whether it also protects against olfactory dysfunction in such women. A total of three olfactory and 12 neurocognitive tests were administered to 432 healthy postmenopausal women with varied HRT histories.

Modeling and simulation approach to support dosing and study design requirements for treating HIV-related neuropsychiatric disease with the NK1-R antagonist aprepitant.

Psychiatric illness is common in HIV-infected patients and underlines the importance for screening not only for cognitive impairment but also for co-morbid mental disease. The rationale for combining immunomodulatory neurokinin- 1 receptor (NK1-R) antagonists with combined antiretroviral therapy (cART) is based on multimodal pharmacologic mechanisms. The NK1-R antagonist aprepitant's potential utility as a drug for depression is complicated by >99.

The glucocorticoid antagonist RU-486 suppresses HIV infectivity and replication.

The effects of RU-486, a glucocorticoid antagonist, on HIV infection and replication in depressed and nondepressed women were studied using ex vivo models of HIV infection. RU-486 treatment of cells decreased HIV reverse transcriptase activity of monocyte-derived macrophages in a model of acute infectivity. RU-486 also decreased HIV viral replication in the chronically-infected T-cell line ACH-2, but not in the promonocyte cell line U1.

Immune suppression and immune activation in depression.

Depression has been characterized as a disorder of both immune suppression and immune activation. Markers of impaired cellular immunity (decreased natural killer cell cytotoxicity) and inflammation (elevated IL-6, TNFα, and CRP) have been associated with depression. These immunological markers have been associated with other medical illnesses, suggesting that immune dysregulation may be a central feature common to both depression and to its frequent medical comorbidities.

Selective serotonin reuptake inhibitor suppression of HIV infectivity and replication.

Objective: To test the hypothesis that the selective serotonin reuptake inhibitor (SSRI) citalopram would down-regulate human immunodeficiency virus (HIV) infectivity and that the greatest effects would be seen in people with depression. Depression is a risk factor for morbidity and mortality in HIV/acquired immune deficiency syndrome. Serotonin (5-HT) neurotransmission has been implicated in the pathobiology of depression, and pharmacologic therapies for depression target this system.

Neurokinin 1 receptor isoforms and the control of innate immunity.

Substance P is the prototype tachykinin peptide and triggers a variety of biological effects in both the nervous and immune system. Two naturally occurring variants of the neurokinin 1 receptor (NK1R) mediate the effects of SP: a 'classic' full-length receptor and a truncated (tail-less) form that lacks 96 amino acid residues at the C-terminus. Most research has focused on the full length receptor and the truncated NK1R has not been extensively explored.

Elevated substance P levels in HIV-infected women in comparison to HIV-negative women.

Substance P and its receptor (neurokinin-1R) are potent modulators of neuroimmunoregulation and HIV/AIDS infection. We previously demonstrated that HIV-seropositive men had significantly higher substance P levels compared to uninfected controls. We now demonstrate that substance P plasma levels are significantly higher in HIV-infected women in comparison to uninfected control women.

Medical co-morbidity in depressive disorders.

Background: Depression is much more prevalent among those with chronic medical conditions compared to the general population of the United States. Depression is recognized as a cause of increased morbidity and mortality and has been associated with higher health care costs, adverse health behaviors, significant functional impairment, lost work productivity, occupational disability and increased health care utilization.

Method: Searches of Medline, OVIDMedline, PubMed and PsycINFO of all English-language articles published between 1966 and 2007 were conducted using the keywords mood disorders, medical comorbidity, depression, antidepressant therapy.

Coadministration of modafinil and a selective serotonin reuptake inhibitor from the initiation of treatment of major depressive disorder with fatigue and sleepiness: a double-blind, placebo-controlled study.

Background: Previous studies suggest that adjunctive modafinil treatment provides benefit for patients with depression with significant sleepiness and fatigue.

Methods: We conducted a multisite, double-blind, placebo-controlled study of the treatment of major depression characterized by excessive sleepiness and fatigue, adding adjunctive modafinil or placebo to a selective serotonin reuptake inhibitor from the beginning of treatment. Seventy-three of 90 consenting patients met all screening criteria to begin treatment with open-label selective serotonin reuptake inhibitor therapy and double-blind addition of either modafinil (100 mg/d for 1 week then 200 mg/d) or matching placebo for 6 weeks.

Selective serotonin reuptake inhibitor and substance P antagonist enhancement of natural killer cell innate immunity in human immunodeficiency virus/acquired immunodeficiency syndrome.

Background: Natural killer (NK) cells play an important role in innate immunity and are involved in the host defense against human immunodeficiency virus (HIV) infection. This study examines the potential role of three underlying regulatory systems that have been under investigation in central nervous system research as well as immune and viral research: serotonin, neurokinin, and glucocorticoid systems.

Methods: Fifty-one HIV-seropositive subjects were recruited to achieve a representative sample of depressed and nondepressed women.

A double-blind, multicenter, parallel-group study of paroxetine, desipramine, or placebo in breast cancer patients (stages I, II, III, and IV) with major depression.

Objective: This study compared the efficacy and safety of paroxetine and desipramine with those of placebo in the treatment of depressive disorders in adult women with breast cancer, stages I-IV.

Method: In a double-blind, placebo-controlled study, 35 female outpatients with breast cancer and DSM-III-R major depression or adjustment disorder with depressed mood were randomly assigned to treatment with paroxetine (N=13), desipramine (N=11), or placebo (N=11) for 6 weeks. Primary efficacy was assessed by change from baseline in score on the 21-item Hamilton Rating Scale for Depression (HAM-D), and the secondary outcome measure was change from baseline in the Clinical Global Impressions-Severity of Illness scale (CGI-S) score.

Association of resolution of major depression with increased natural killer cell activity among HIV-seropositive women.

Objective: Depression is a potential risk factor for morbidity and mortality among patients with numerous medical conditions, including HIV disease, and it is also associated with decrements in immune function, such as natural killer (NK) cell activity. This study examined whether improvements in the diagnostic status of major depression are related to increases in NK cell activity among HIV-seropositive women.

Method: HIV-seropositive women were recruited as part of a longitudinal cohort study and underwent comprehensive medical and psychiatric evaluations during a 2-year period.

Corticosterone modulates auditory gating in mouse.

Previous studies suggest that circulating glucocorticoids may influence the encoding and processing of sensory stimuli. The current study investigated this hypothesis by measuring the generation (amplitude), gating (recovery cycle), and sensitivity (intensity function) of auditory evoked responses in C57BL/6 mice treated with chronic corticosterone (0, 1, 5, 15, or 30 mg/kg/day for 14 days). We found that low-dose corticosterone (5 but not 1 mg/kg/day) enhanced the amplitude and improved gating of evoked potentials without affecting the intensity function.

Mood disorders in the medically ill: scientific review and recommendations.

Objective: The purpose of this review is to assess the relationship between mood disorders and development, course, and associated morbidity and mortality of selected medical illnesses, review evidence for treatment, and determine needs in clinical practice and research.

Data Sources: Data were culled from the 2002 Depression and Bipolar Support Alliance Conference proceedings and a literature review addressing prevalence, risk factors, diagnosis, and treatment. This review also considered the experience of primary and specialty care providers, policy analysts, and patient advocates.

Neuropsychiatric manifestations of HIV infection and AIDS.

As the life expectancy of people living with HIV infection has increased (through recent advances in antiretroviral therapy), clinicians have been more likely to encounter neuropsychiatric manifestations of the disease. Some patients present with cognitive deficits due to an HIV-triggered neurotoxic cascade in the central nervous system. However, more patients present with a depressive spectrum disorder during the course of their illness, the underlying pathogenesis of which is not as well understood.

The role of stress-induced cortisol in the relationship between depression and decreased bone mineral density.

Background: This study was designed to test the hypothesis that cortisol mediates the relationship between bone density and depression in postmenopausal women.

Methods: Nineteen women aged 52-79 who had been assessed for bone mineral density by dual-energy x-ray absorptiometer (DEXA) were evaluated for depression and anxiety. Diurnal and stress-induced measures of salivary cortisol were obtained during the following week and at a laboratory session involving a speech task.