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Biomedical subjects

Dwight L Evans

Publications and source records attributed to Dwight L Evans.

At least 19 recordsLinked to original sources

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. In comparison, higher doses (15 and 30 mg/kg/day) decreased the amplitude and impaired gating of evoked potentials, also without altering the stimulus intensity function. At all doses, lower amplitudes of evoked potentials were significantly correlated with higher circulating corticosterone levels. These data highlight the need to consider serum glucocorticoid levels when assessing human disease states associated with aberrations of information processing such as schizophrenia and depression.

Animals↗

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. RESULTS: Mean changes in the total HAM-D and CGI-S scores from baseline to 6-week endpoint for the paroxetine and desipramine groups were not significantly different than those for the placebo-treated group. An unusually high rate of response (defined as >or=50% improvement in the HAM-D score) in the placebo group was observed (55% [N=6]); adverse events precipitated patient discontinuation in the active treatment groups (9% [N=1] for desipramine, 15% [N=2] for paroxetine) similar to that in the placebo-treated patients (18% [N=2]). Improvement on symptom dimensions within the HAM-D and Hamilton Rating Scale for Anxiety (depressive, anxiety, cognitive, neurovegetative, or somatic) was also similar between groups. CONCLUSION: The small number of women in this study most likely contributed to the lack of observed differences in efficacy observed during the 6 weeks of treatment. Randomized, placebo-controlled trials of adequate power seeking to determine efficacy of antidepressants in the United States for the treatment of women with breast cancer and comorbid depression remain of paramount importance.

Adult↗

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. The review and recommendations reflect the expert opinion of the authors. STUDY SELECTION/DATA EXTRACTION: Reviews of epidemiology and mechanistic studies were included, as were open-label and randomized, controlled trials on treatment of depression in patients with medical comorbidities. Data on study design, population, and results were extracted for review of evidence that includes tables of prevalence and pharmacological treatment. The effect of depression and bipolar disorder on selected medical comorbidities was assessed, and recommendations for practice, research, and policy were developed. CONCLUSIONS: A growing body of evidence suggests that biological mechanisms underlie a bidirectional link between mood disorders and many medical illnesses. In addition, there is evidence to suggest that mood disorders affect the course of medical illnesses. Further prospective studies are warranted.

Acquired Immunodeficiency Syndrome↗

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. RESULTS: Nine volunteers reported depression while 10 were never depressed. Ever depressed women had significantly lower total lumbar and right femur DEXA Z scores than never depressed (t(17) = 2.5, p = .019 and t(17) = 2.06, p = .05, respectively). Ever depressed women demonstrated a significant increase in salivary cortisol (area under the curve (AUC) = 27.83, SD = 37.64) compared to never depressed women (AUC = -13.34, SD = 19.55) (t(17) = -3.041, p = .007) during a psychological challenge. There were significant inverse relationships between salivary cortisol AUC values and bone density Z scores at every measured bone site. Mediation analyses suggest that 51 - 67% of the association between depression and bone density could be attributed to stress-induced changes in cortisol. CONCLUSIONS: Cortisol hypersecretion in response to stress may, in part, explain the impact of depression on bone density in post-menopausal women.

Absorptiometry, Photon↗

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. Fifty-seven women had complete NK cell activity and depression data measured at two time points and were examined for associations between changes in depression status and alterations in NK cell activity over time. RESULTS: Among the 57 HIV-seropositive women, improvements in the diagnostic status of depression and decreases in scores on the 17-item Hamilton Depression Rating Scale were significantly associated with increases in NK cell activity over time, as measured in lytic units. Eleven women (19.3%) had a major depression diagnosis that resolved over time, and this group also had a significant increase in cell activity measured in lytic units during this period. CONCLUSIONS: This study suggests that depression may impair certain aspects of innate cellular immunity relevant to delaying the progression of HIV disease and that these alterations are reversible with the resolution of a depressive episode. These findings support an examination of NK cell activity in assessments of the relationship between depression and morbidity and mortality in HIV disease.

Adult↗

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. This category of psychiatric disorders presents diagnostic challenges because of the many neurovegetative confounding factors that are present in association with HIV illness. As quality of life becomes a more central consideration in the management of this chronic illness, better awareness of these neuropsychiatric manifestations is paramount. This article reviews these clinical issues and the available psychopharmacologic treatment options.

Acquired Immunodeficiency Syndrome↗

Changes in neuropsychological functioning with progression of HIV-1 infection: results of an 8-year longitudinal investigation.

Despite the advent of more effective treatments for HIV-1 infection, cognitive impairment is still frequent and questions remain regarding which areas of impairment are more common in the different disease stages. This study investigated cognitive performance over an 8-year period of time in 59 HIV-1 seropositive (HIV-1+) men who were clinically asymptomatic at study entry, in comparison to a cohort of 55 HIV-1 seronegative (HIV-1-) men. Every 6 months we examined cognitive functioning in 5 domains-fine motor speed, attention, verbal memory, executive functioning, and speed of information processing. We found that patients with AIDS scored significantly worse on fine motor speed and speed of information processing than HIV-1- individuals and the HIV-1+ non-AIDS patients. In addition, the HIV-1+ non-AIDS patients performed more poorly than the HIV-1- group on speed of information processing. Depressive symptoms were also associated with diminished performance on measures of attention, executive functioning, and speed of information processing. Further research is needed to examine the effects of disease stage and depression on cognitive impairment in the era of new HIV treatments.

AIDS Dementia Complex↗

Treatment outcome and physician-patient communication in primary care patients with chronic, recurrent depression.

OBJECTIVE: The authors' goal was to assess the adequacy of control, quality of life, and treatment experiences of patients with chronic, recurrent depression being treated by primary care physicians. METHOD: The sample comprised 1,001 patients 18 years old or older who had chronic, recurring depression and were currently being treated with a single antidepressant prescribed by a primary care physician. These patients had responded positively to questions regarding the presence of clinical depression and prescription of a single antidepressant by a primary care physician during a telephone survey conducted in two stages separated by 18 to 24 months. The 1,001 patients participated in a structured, 20-minute, anonymous interview conducted by trained personnel. RESULTS: Most patients had recurrent depression (median=5 episodes), and most had taken their current antidepressant for more than 1 year. The mean age at onset of depression was 33.8 years, and the mean age at time of diagnosis was 38.0 years, with treatment following a mean of 2 years later. Most patients were satisfied with the care they received from their primary care physician, but many also reported incomplete symptom resolution and substantial side effects from medications that were not discussed with or by their primary care physician. A majority of patients reported that treatment decisions were made in conjunction with their physician, a method that was preferred by three-quarters of the group. Although 752 patients reported that they had mild or moderate depression, 729 were satisfied with their life and 600 said they were in good or excellent health. CONCLUSIONS: Despite being mostly satisfied with the care received from their primary care physician, patients with chronic, recurring depression had substantial levels of continuing dysfunction, distress, unrelieved symptoms, and medication side effects, which suggests several possible physician-centered, patient-centered, or system-centered barriers to treatment to full function and wellness.

Adolescent↗

Prevalence, diagnosis, and pharmacological treatment of mood disorders in HIV disease.

Human immunodeficiency virus seropositive (HIV+) individuals are at a heightened risk of developing mood disorders and related syndromes. Over the past several decades, increased rates of mood disorders, including depression and mania, have been reported among HIV+ individuals. Because alterations in mood may impact on quality of life and perhaps reduce adherence to antiretroviral treatment regimens that are critical for preventing disease progression, recognition and effective treatment of mood disorders is essential. There are accumulating data showing that antidepressants and mood stabilizers, as well as other novel agents, might benefit HIV+ individuals suffering from a concomitant mood disturbance. This review highlights the relevant studies that have examined prevalence rates of mood disorders in HIV+ individuals, characteristics of HIV disease that influence the diagnosis and psychopharmacologic treatment of mood disorders, including complex interactions with antiretroviral medications, as well as the available evidence regarding the efficacy of agents used to treat depression and mania in the context of HIV disease.

Antidepressive Agents↗

Maintenance efficacy of divalproex in the prevention of bipolar depression.

Breakthrough depression is a common problem in the treatment of bipolar disorder. Only one, recently published, double-blind, placebo-controlled trial has examined the efficacy of divalproex in the prevention of depressive episodes in bipolar patients. This report describes, in further detail, the findings from that trial of the effect of divalproex on multiple dimensions of depressive morbidity in bipolar disorder. A randomized, double-blind, parallel-group, multicenter study was conducted over a 52-week maintenance period. Bipolar I patients, who may have been treated with open-label lithium or divalproex and who met recovery criteria within 3 months of onset of an index manic episode, were randomized to maintenance treatment with divalproex, lithium, or placebo in a 2 : 1 : 1 ratio. Adjunctive paroxetine or sertraline for breakthrough depression was allowed in maintenance phase. Outcome measures were the rate of early discontinuation for depression, time to depressive relapse, proportion of patients with depressive relapse, mean change in Depressive Syndrome Scale score, proportion of patients receiving antidepressants, and time in the study. Among patients taking an antidepressant, a higher percentage of patients on placebo than divalproex discontinued early for depression. Patients who were previously hospitalized for affective episodes or took divalproex in the open period relapsed later on divalproex than on lithium during the maintenance period. Divalproex-treated patients had less worsening of depressive symptoms than lithium-treated patients during maintenance. Indices of severity of prestudy illness course predicted worse outcome in all treatment groups. Divalproex improved several dimensions of depressive morbidity and reduced the probability of depressive relapse in bipolar disorder, particularly in patients who had responded to divalproex when manic, and among patients with a more severe course of illness.

Adolescent↗

Association of depression, CD8+ T lymphocytes, and natural killer cell activity: implications for morbidity and mortality in Human immunodeficiency virus disease.

A heightened risk of mood disorders, such as major depression, and acute depressive symptoms has been observed among HIV-seropositive individuals since the start of the AIDS epidemic, and an accumulating body of data now shows that depression may have an impact on morbidity and mortality among individuals with HIV disease. Although the specific physiologic mechanisms involved in this process have not been delineated, there is some evidence to suggest that certain components of innate immunity, including killer lymphocytes such as CD8+ T lymphocytes and natural killer cells, may represent key pathways through which depression affects HIV disease progression. This paper reviews some of the main studies examining the effects of depression on immunity and HIV disease progression and discusses the potential role of killer lymphocytes as an underlying mechanism by which depression may impact morbidity and mortality.

CD8-Positive T-Lymphocytes↗

Depression and HIV infection: impact on immune function and disease progression.

Can psychological factors, such as depression, affect human immunodeficiency virus progression? HIV infection is viewed as a chronic illness in which those infected often confront a number of emotional challenges and physical health and disease-related issues. Over the past 20 years, there has been increasing evidence that depression and other mood-related disturbances are commonly observed among HIV-positive individuals. There is also mounting data showing that depressive symptoms might further impact upon specific elements of immune system functioning and influence quality of life and health status. This paper will highlight studies examining the prevalence of depression during HIV infection and review some of the evidence examining the impact of depressive symptoms on immune function and HIV disease progression.

CD4 Lymphocyte Count↗

Neuropsychopharmacologic treatment of depression and other neuropsychiatric disorders in HIV-infected individuals.

How can neuropsychiatric disorders and syndromes be underdiagnosed and inadequately treated in individuals infected with human immunodeficiency virus? Depression in particular is among the most prevalent diagnoses and there is a solid foundation of data from controlled clinical studies that has begun to examine the efficacy of various antidepressants in HIV-infected persons. This article summarizes essential findings pertaining to the use of psychotropic medications to treat depression and other neuropsychiatric disorders in the context of immunodeficiency. This includes discussion of clinically significant treatment considerations (eg, efficacy, side effects, drug-drug interactions) derived from the existing literature. Taken together, there is compelling evidence that psychopharmacologic intervention can improve the quality of life of mentally ill HIV-infected individuals.

AIDS Dementia Complex↗

National Depressive and Manic-Depressive Association consensus statement on the use of placebo in clinical trials of mood disorders.

A consensus conference on the use of placebo in mood disorder studies consisted of expert presentations on bioethics, biostatistics, unipolar depression, and bipolar disorder. Work groups considered evidence and presented statements to the group. Although it was not possible to write a document for which there was complete agreement on all issues, the final document incorporated input from all authors. There was consensus that placebo has a definite role in mood disorder studies. Findings of equivalence between a new drug and standard treatment in active control studies is not evidence of efficacy unless the new drug is also significantly more effective than placebo. Add-on studies in which patients are randomized to standard therapy plus the investigational drug or standard therapy plus placebo are especially indicated for high-risk patients. Mood disorders in elderly and pediatric patients are understudied, and properly designed trials are urgently needed. Research is needed on the ethical conduct of studies to limit risks of medication-free intervals and facilitate poststudy treatment. Patients must fully understand the risks and lack of individualized treatment involved in research.

Bipolar Disorder↗

Substance P and Human Immunodeficiency Virus Infection: Psychoneuroimmunology.

Effects on the immune system caused by changes in behavioral state or brain activity are mediated, at least in part, through neuroendocrine-immune pathways. Life stress and depression may be associated with altered blood levels of central nervous system-released neuropeptides, including substance P (SP). SP acts as a neuroregulator or neurotransmitter in the conduction of nociceptive stimuli, and is a modulator of neuroimmunoregulation. This review summarizes current knowledge regarding the role of the neuropeptide, SP, in psychoneuroimmunology, in particular as it relates to human immunodeficiency virus infection and acquired immunodeficiency disease syndrome. The association between depression, anxiety, and stress in HIV-disease progression suggests that neurobiologic and neurophysiologic factors play a role in modulating HIV infection and responses to antiretroviral therapy. Individuals with HIV or AIDS may experience stressful life circumstances that can result in increased symptoms of anxiety, stress, and/or depression. Furthermore, psychological and psychiatric symptoms, which occur in individuals with HIV and AIDS, may be related to the progression of AIDS disease. This review presents evidence from the literature, as well as findings from basic investigations conducted in the authors' laboratories, demonstrating that SP may play an important role in HIV pathophysiology. SP can impact the susceptibility of immune cells to HIV infection and modulate immune cell functions in ways that may affect the course of HIV in infected individuals. Moreover, modulation of SP activity and SP receptor is being explored for its potential as a novel therapeutic approach to the treatment of some psychological and psychiatric disorders and to the design of new anti-HIV therapy.

Journal Article↗

Association of depression with viral load, CD8 T lymphocytes, and natural killer cells in women with HIV infection.

OBJECTIVE: Clinical and epidemiology studies have implicated depression as a risk factor in the morbidity and mortality of many human diseases. This study sought to determine if depression was associated with alterations in cellular immunity variables-specifically, natural killer (NK) cells and CD8 T lymphocytes-in women with HIV infection. METHOD: Ninety-three women (63 HIV-seropositive, 30 HIV-seronegative) were studied as part of an ongoing longitudinal study conducted at two sites. Subjects underwent extensive clinical, psychiatric, and immunological evaluations. CBC counts and flow cytometry panels were conducted and NK cell activity assayed for all subjects; viral load was determined for HIV-seropositive subjects. RESULTS: The overall rate of major depression in the HIV-seropositive and HIV-seronegative women was 15.87% (N=10 of 63) and 10.00% (N=3 of 30), respectively. HIV-seropositive women had higher depressive symptom scores than did the comparison subjects (Hamilton depression scale: mean=8.62 [SD=7.26] versus mean=5.67 [SD=7.33], respectively). Both groups had similar anxiety scores. Depressive and anxiety symptoms were significantly associated with higher activated CD8 T lymphocyte counts and higher viral load levels. Major depression was associated with significantly lower natural killer cell activity, and depressive and anxiety symptom scores showed a similar correlation. CONCLUSIONS: Our findings provide the first evidence that depression may alter the function of killer lymphocytes in HIV-infected women and suggest that depression may decrease natural killer cell activity and lead to an increase in activated CD8 T lymphocytes and viral load. The rate of current major depression in these HIV-seropositive women (none of whom had current substance abuse) is approximately twice that reported for HIV-seropositive men. The rate is also consistent with studies of women with other medical illnesses and with a recent epidemiology study that associated depression with mortality in HIV-infected women with chronic depressive symptoms. Depression may have a negative impact on innate immunity. Examination of killer lymphocytes may prove useful in assessing the potential relationship between depression, immunity, and HIV disease progression in women.

Adult↗

Depressive and anxiety disorders in women with HIV infection.

OBJECTIVE: This study examined whether there were differences in the rate of depressive and anxiety disorders between HIV-infected women (N=93) and a comparison group of uninfected women (N=62). Secondary objectives were to examine correlates of depression in HIV-infected women-including HIV disease stage and protease inhibitor use-and the associations between symptoms of depression or anxiety and other potential predictor variables. METHOD: Subjects underwent extensive semiannual clinical, psychiatric, neuropsychological, and immunological evaluations. Depressive and anxiety disorder diagnoses were assessed by using the Structured Clinical Interview for DSM-IV. Symptoms of depression and anxiety were evaluated with the Hamilton Depression Rating Scale (the 17-item version and a modified 11-item version) and the Hamilton Anxiety Rating Scale, respectively. RESULTS: The rate of current major depressive disorder was four times higher in HIV-seropositive women (19.4%) than in HIV-seronegative women (4.8%). Mean depressive symptom scores on the 17-item Hamilton depression scale also were significantly higher, overall, in the HIV-infected women (mean=8.7, SD=8.0) relative to comparison subjects (mean=3.3, SD=5.8). There was no significant between-group difference in the rate of anxiety disorders. However, HIV-seropositive women had significantly higher anxiety symptom scores (mean=8.8, SD=8.9) than did HIV-seronegative women (mean=3.6, SD=5.5). Both groups had similar substance abuse/dependence histories, but adjusting for this factor had little impact on the relationship of HIV status to current major depressive disorder. CONCLUSIONS: HIV-seropositive women without current substance abuse exhibited a significantly higher rate of major depressive disorder and more symptoms of depression and anxiety than did a group of HIV-seronegative women with similar demographic characteristics. These controlled, clinical findings extend recent epidemiologic findings and underscore the importance of adequate assessment and treatment of depression and anxiety in HIV-infected women.

Adolescent↗