Robert N. Golden

Bio: Robert N. Golden is an academic researcher from University of Wisconsin-Madison. The author has contributed to research in topics: Clomipramine & Depression (differential diagnoses). The author has an hindex of 48, co-authored 173 publications receiving 9008 citations. Previous affiliations of Robert N. Golden include National Institutes of Health & University of North Carolina at Chapel Hill.

The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence.

Abstract: Objective: The purpose of this study was to assess the evidence base for the efficacy of light therapy in treating mood disorders. Method: The authors systematically searched PubMed (January 1975 to July 2003) to identify randomized, controlled trials of light therapy for mood disorders that fulfilled predefined criteria. These articles were abstracted, and data were synthesized by disease and intervention category. Results: Only 13% of the studies met the inclusion criteria. Meta-analyses revealed that a significant reduction in depression symptom severity was associated with bright light treatment (eight studies, having an effect size of 0.84 and 95% confidence interval [CI] of 0.60 to 1.08) and dawn simulation in seasonal affective disorder (five studies; effect size=0.73, 95% CI=0.37 to 1.08) and with bright light treatment in nonseasonal depression (three studies; effect size=0.53, 95% CI=0.18 to 0.89). Bright light as an adjunct to antidepressant pharmacotherapy for nonseasonal depression was not effective (five studies; effect size= –0.01, 95% CI=–0.36 to 0.34). Conclusions: Many reports of the efficacy of light therapy are not based on rigorous study designs. This analysis of randomized, controlled trials suggests that bright light treatment and dawn simulation for seasonal affective disorder and bright light for nonseasonal depression are efficacious, with effect sizes equivalent to those in most antidepressant pharmacotherapy trials. Adopting standard approaches to light therapy’s specific issues (e.g., defining parameters of active versus placebo conditions) and incorporating rigorous designs (e.g., adequate group sizes, randomized assignment) are necessary to evaluate light therapy for mood disorders. (Am J Psychiatry 2005; 162:656–662) T he development of light therapy in psychiatry is closely intertwined with the original description of the syndrome of seasonal affective disorder. Two decades ago, Rosenthal and colleagues (1) described a series of patients with histories of recurrent depressions that developed in the fall or winter and spontaneously remitted during the following spring or summer. Their initial report also included preliminary findings indicating that bright artificial light, administered in a manner that would in essence extend the photoperiod, was more effective than dim light in treating seasonal affective disorder. The article presented an underlying hypothesis about the pathophysiology of the syndrome (i.e., depressogenic effects of melatonin), which in turn shaped the selection of treatment parameters: the intensity, duration, and timing of bright light exposure were designed to suppress the release of melatonin and lengthen the photoperiod. Both seasonal affective disorder and bright light therapy quickly captured considerable attention, both in the scientific community and with the general public. Several research groups launched clinical trial programs, and soon this experimental treatment was extended to other conditions, including nonseasonal mood disorders, Alz

Bupropion: a review of its mechanism of antidepressant activity.

Abstract: Background The mechanism of action of the novel antidepressant bupropion remains unclear after many years of study. A review of the relevant biochemical, in vivo brain microdialysis, electrophysiologic, behavioral, and clinical data clarifies what is known about this unique compound and suggests possible modes of action. Method A panel of 11 experts was convened for a conference to discuss bupropion's mechanism of antidepressant activity. Four of the panelists presented current research findings, followed by a discussion. Results (1) Biochemical studies suggest down-regulation of postsynaptic beta-adrenoceptors and desensitization of the norepinephrine-stimulated adenylate cyclase in the rat cortex occur only after chronic administration of very high doses of bupropion. (2) In vivo brain microdialysis studies demonstrate that, after chronic administration, there is an enhancement of bupropion-induced increases in extracellular dopamine in the nucleus accumbens. (3) Electrophysiologic data show that with acute dosing, bupropion reduces the firing rates of noradrenergic neurons in the locus ceruleus. The firing rates of dopaminergic neurons are reduced by bupropion in the A9 and A10 areas of the brain, but only at very high doses, and bupropion does not alter the firing rates of serotonergic neurons in the dorsal raphe. (4) Behavioral studies show that the most active metabolite of bupropion, hydroxybupropion (306U73), appears to be responsible for a large part of the compound's effects in animal models of antidepressant activity. (5) Clinical studies indicate that bupropion enhances noradrenergic functional activity as reflected by an increased excretion of the hydroxy metabolite of melatonin, while at the same time producing a presumably compensatory decrease in norepinephrine turnover. In one study, bupropion elevated plasma levels of the dopamine metabolite homovanillic acid in nonresponders, but not in responders. Conclusion The mechanism of action of bupropion appears to have an unusual, not fully understood, noradrenergic link. The bupropion metabolite hydroxybupropion probably plays a critical role in bupropion's antidepressant activity, which appears to be predominantly associated with long-term noradrenergic effects. The mild central nervous system activating effects of bupropion appear to be due to weak dopaminergic mechanisms. There is some evidence that dopamine may contribute to bupropion's antidepressant properties. Antidepressant effects of bupropion are not serotonergically mediated.

Progression to AIDS: the effects of stress, depressive symptoms, and social support.

Abstract: OBJECTIVE We examined the effects of stress, depressive symptoms, and social support on the progression of HIV infection. METHODS Eighty-two HIV-infected gay men without symptoms or AIDS at baseline were followed up every 6 months for up to 5.5 years. Men were recruited from rural and urban areas in North Carolina as part of the Coping in Health and Illness Project. Disease progression was defined using criteria for AIDS (CD4+ lymphocyte count of <200/microl and/or an AIDS-indicator condition). RESULTS We used Cox regression models with time-dependent covariates, adjusting for age, education, race, baseline CD4+ count, tobacco use, and number of antiretroviral medications. Faster progression to AIDS was associated with more cumulative stressful life events (p = .002), more cumulative depressive symptoms (p = .008), and less cumulative social support (p = .0002). When all three variables were analyzed together, stress and social support remained significant in the model. At 5.5 years, the probability of getting AIDS was about two to three times as high among those above the median on stress or below the median on social support compared with those below the median on stress or above the median on support, respectively. CONCLUSIONS These data are among the first to demonstrate that more stress and less social support may accelerate the course of HIV disease progression. Additional study will be necessary to elucidate the mechanisms that underlie these relationships and to determine whether interventions that address stress and social support can alter the course of HIV infection.

Impact of Stressful Life Events, Depression, Social Support, Coping, and Cortisol on Progression to AIDS

Abstract: OBJECTIVE: This study examined prospectively the effects of stressful events, depressive symptoms, social support, coping methods, and cortisol levels on progression of HIV-1 infection. METHOD: Eighty-two homosexual men with HIV type-1 infection without AIDS or symptoms at baseline were studied every 6 months for up to 7.5 years. Men were recruited from rural and urban areas in North Carolina, and none was using antiretroviral medications at entry. Disease progression was defined as CD4+ lymphocyte count <200/μl or the presence of an AIDS indicator condition. RESULTS: Cox regression models with time-dependent covariates were used adjusting for race, baseline CD4+ count and viral load, and cumulative average antiretroviral medications. Faster progression to AIDS was associated with higher cumulative average stressful life events, coping by means of denial, and higher serum cortisol as well as with lower cumulative average satisfaction with social support. Other background (e.g., age, education) and health ...

Principles of Neural Science

Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Psychological Stress and the Human Immune System: A Meta-Analytic Study of 30 Years of Inquiry

Abstract: The present report meta-analyzes more than 300 empirical articles describing a relationship between psychological stress and parameters of the immune system in human participants. Acute stressors (lasting minutes) were associated with potentially adaptive upregulation of some parameters of natural immunity and downregulation of some functions of specific immunity. Brief naturalistic stressors (such as exams) tended to suppress cellular immunity while preserving humoral immunity. Chronic stressors were associated with suppression of both cellular and humoral measures. Effects of event sequences varied according to the kind of event (trauma vs. loss). Subjective reports of stress generally did not associate with immune change. In some cases, physical vulnerability as a function of age or disease also increased vulnerability to immune change during stressors.

The molecular neurobiology of depression

Abstract: Unravelling the pathophysiology of depression is a unique challenge. Not only are depressive syndromes heterogeneous and their aetiologies diverse, but symptoms such as guilt and suicidality are impossible to reproduce in animal models. Nevertheless, other symptoms have been accurately modelled, and these, together with clinical data, are providing insight into the neurobiology of depression. Recent studies combining behavioural, molecular and electrophysiological techniques reveal that certain aspects of depression result from maladaptive stress-induced neuroplastic changes in specific neural circuits. They also show that understanding the mechanisms of resilience to stress offers a crucial new dimension for the development of fundamentally novel antidepressant treatments.