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Biomedical subjects

R N Golden

Publications and source records attributed to R N Golden.

At least 55 records · Page 3Linked to original sources

Mood disorders in HIV infection: prevalence and risk factors in a nonepicenter of the AIDS epidemic.

OBJECTIVE: The authors studied the lifetime, initial cross-sectional, and 6-month follow-up prevalence of mood disorders in asymptomatic HIV-infected and uninfected homosexual men who lived in an area with a low prevalence of HIV. They also determined the relationship between current major depression and potential depression risk factors. METHOD: Subjects included 98 asymptomatic HIV-infected and 71 uninfected homosexual men. Subjects underwent extensive clinical, psychiatric, neuropsychological, and laboratory evaluations. RESULTS: Similar proportions of HIV-infected and uninfected subjects reported a lifetime (29% and 45%, respectively), an initial current (8% and 3%), and a 6-month follow-up (9% and 11%) history of major depressive disorder. Anxiety disorders were less common, with similar proportions of HIV-infected and uninfected subjects reporting a lifetime (7% and 13%, respectively), an initial current (3% and 7%), and a 6-month follow-up (2% and 5%) history of anxiety disorders. There were no differences in the severity of mood symptoms between HIV-infected and uninfected subjects. Current major depression at initial visit was significantly associated with lifetime history of major depression but not with neuropsychological function or vitamin B12 level. CONCLUSIONS: These findings are in agreement with previous studies of areas with a high prevalence of HIV. However, the proportion of subjects with mood disorders is high compared with general population studies. Both HIV-infected and uninfected homosexual men may be at high risk for major depression, especially if they have a past history of depression. Moreover, in the asymptomatic stage of HIV infection, major depression does not appear to be secondary to HIV central nervous system effects or low vitamin B12 levels.

Acquired Immunodeficiency Syndrome↗

Altered prolactin response to clomipramine rechallenge in healthy subjects.

The effect of an initial challenge with the serotonin (5-HT) uptake inhibitor clomipramine (CMI) on subsequent rechallenge was studied in healthy men who served as volunteers. Carefully screened volunteers were assigned to one of three conditions: (1) CMI challenge followed 2 weeks later by CMI rechallenge; (2) placebo challenge followed 2 weeks later by CMI challenge; and (3) CMI challenge followed 4 weeks later by CMI rechallenge. We found significant blunting of the prolactin response to CMI rechallenge 2 weeks (Signed Rank = -12, p = 0.05), but not 4 weeks after an initial challenge. Placebo challenge did not effect CMI challenge 2 weeks later. These findings suggest that a single exposure to IV CMI may cause 5-HT receptor changes that are present 2, but not 4 weeks later. The ramifications of this finding with regard to the use of 5-HT challenge paradigms in a test-retest design are discussed.

Adolescent↗

Central serotonergic changes following antidepressant treatment: a neuroendocrine assessment.

We employed a neuroendocrine challenge paradigm to study the effects of antidepressant treatment on serotonergic systems in depressed patients. We compared the maximum prolactin response to intravenous clomipramine (CMI) in depressed patients who responded to antidepressant treatment to that of nonresponders. Pretreatment baseline prolactin concentrations and pretreatment prolactin responses to clomipramine challenge were not different in responders compared to non-responders. However, following antidepressant treatment, the 6 responders demonstrated a significant change in their clomipramine challenge test results, as indicated by an increase in prolactin responses. In contrast, the 7 nonresponders did not demonstrate a change in their prolactin response to clomipramine challenge following treatment. These data support the hypothesis that serotonergic system dysfunction, as manifested by blunted prolactin response to clomipramine challenge, tends to normalize after successful treatment for depression, and that abnormal serotonergic function may be a state-dependent characteristic.

Adolescent↗

Circulating natural killer cell phenotypes in men and women with major depression. Relation to cytotoxic activity and severity of depression.

The effects of major depression on peripheral blood natural killer cell phenotypes and natural killer cell activity were studied by comparing depressed and normal control subjects. Depressed subjects exhibited (1) significant reductions in Leu-11 (CD16) natural killer effector cells and natural killer cell activity and (2) a dissociation of the normal positive correlation between the percentage of Leu-11 cells and natural killer cell activity. These findings suggest that alterations in the availability and the killing capacity of circulating Leu-11 natural killer cells appear to be responsible for depression-related reductions in natural killer cell activity. Moreover, men with major depression showed marked reductions in Leu-11 cells, natural killer cell activity, and Leu-7 (HNK-1) lymphocytes compared with normal control men. By contrast, depressed women did not differ significantly from normal control women on any of these three immune function measures. Severity of depression as assessed by Hamilton Rating Scale for Depression scores was not associated with natural killer cell activity or Leu-7 lymphocyte levels in either men or women with major depression. Hamilton Rating Scale for Depression severity ratings were, however, strongly inversely correlated with Leu-11 lymphocyte counts among men, but not women, with major depression. These data begin to elucidate the immunological mechanisms by which natural killer cell activity is altered in depression and suggest that some measures of immunity may be differentially affected in male and female subjects with the syndrome of major depression.

Adolescent↗

In vivo phosphorus NMR spectroscopy of skin using a crossover surface coil.

A modified crossover surface coil with minimal B1 field penetration was used for collection of skin phosphorus NMR spectra. Projection imaging experiments show that the coil-sensitive volume is uniform at the phosphorus frequency, but strikingly nonuniform at the proton frequency. Experiments with an in vitro phosphorus phantom, designed to simulate skin and underlying tissue, demonstrated that 45.1% (+/- 1.2%) of total signal was derived from Sprague-Dawley rat skin and 19.3% (+/- 1.4%) of total signal was derived from Fischer-344 rat skin. 31P MR spectra of rat skin in vivo permitted resolution of four phosphorus compounds: nucleoside triphosphates, phosphocreatine (PCr), inorganic phosphate (Pi), and phosphomonoester. Spectra collected after skin flap surgery in Fischer-344 rats showed a 50.1% (+/- 7.6%) reduction in the ratio of PCr/Pi within 30 min of surgery, compared to presurgical PCr/Pi levels (P less than 0.01). Skin phosphorus spectra are potentially useful for assessment of skin flap and skin graft viability.

Animals↗

Magnetic resonance spectroscopic measurement of cellular thiol reduction-oxidation state.

Chromatographic and magnetic resonance spectroscopic measurements of thiol reduction-oxidation state in chemically constructed samples show close analytical agreement. This result, coupled with the synthesis of new probe molecules allowing greater sensitivity and lower toxicity, supports the development of an NMR method for non-invasive thiol redox measurement, an important variable in the response of tumors to radiation and chemotherapy.

Amifostine↗

Neuroendocrine effects of intravenous clomipramine in depressed patients and healthy subjects.

OBJECTIVE: Neuroendocrine challenge paradigms have been used to asses serotonergic systems in depression, but limitations in the specificity of many of these tests have been noted. In this study, the neuroendocrine responses to acute intravenous administration of the serotonin (5-HT) reuptake inhibitor clomipramine were assessed in depressed patients and matched control subjects. METHODS: Thirty hospitalized patients who met DSM-III-R criteria for major depression, and 30 healthy control subjects who were matched for age, sex, and season of year for the time of study, received 12.5 mg of intravenously administered clomipramine. RESULTS: The depressed patients demonstrated significant blunting of prolactin responses to clomipramine, as well as trends toward blunted ACTH and cortisol responses. There was no difference between the patient and control groups in growth hormone responses, plasma clomipramine levels, or self-reports of side effects. CONCLUSIONS: These data support the hypothesis that depressed patients have abnormal neuroendocrine responses to the intravenous administration of the 5-HT reuptake inhibitor clomipramine. Further study is required to delineate the mechanisms responsible for the abnormal response to intravenously administered clomipramine in depression.

Adolescent↗

The detection of depression by patient self-report in women with gynecologic cancer.

We examined the utility of patient self-report forms in identifying those gynecologic oncology patients who would be diagnosed by an experienced consultation-liaison psychiatrist as suffering from major depression. Sixty-five women with gynecologic tumors were evaluated by a consultation-liaison psychiatrist, using standardized (DSM-III) criteria. Each patient also completed a Carroll Rating Scale for Depression (CRS). The CRS demonstrated sensitivity and specificity of 87 percent and 58 percent, respectively. Used as a screening instrument to rule out depression, the CRS yielded a negative predictive value of 94 percent. We identified a priori forty items from the CRS which should not be influenced by the non-psychiatric biologic effects of gynecologic tumors, and compared the performance of this non-cancer related symptoms subscale (NCSG) to that of the CRS. The NCSG did not significantly outperform the CRS; its sensitivity and specificity were 87 percent and 62 percent, respectively. Because our study population was relatively homogeneous (i.e., non-ovarian gynecologic oncology patients without severe debilitation who were not receiving chemotherapy, radiation therapy, or other invasive procedures), the findings should not be generalized to other oncologic populations at this time. Our results suggest that patient self-report forms can be effective screening devices for identifying those non-ovarian, gynecologic oncology patients who should then be carefully evaluated for coexisting clinical depression.

Adult↗

Serotonin, suicide, and aggression: clinical studies.

Both suicidal and aggressive, impulsive behaviors have been linked to putative dysregulation in central serotonergic systems. We review data examining the role of serotonin (5-HT) in suicide from postmortem studies and clinical investigations of suicide attempters, including our own preliminary work derived from neuroendocrine challenges with the 5-HT uptake inhibitor clomipramine. Various approaches to the study of 5-HT and aggressive, impulsive behavior, including cerebrospinal fluid studies, investigations of peripheral measures of 5-HT, and neuroendocrine studies utilizing 5-HT probes, are highlighted. Several important caveats, including the challenge of quantifying "suicidality" and "aggression" in reliable and valid ways, should be considered in interpreting the results of clinical studies of 5-HT and suicide and aggression.

Adolescent↗

Antidepressant challenge tests: the interface of pharmacokinetics and pharmacodynamics.

Antidepressant compounds have been used as probes in neuroendocrine challenge tests designed to assess the functional responsivity of central neurotransmitter systems. Neurohormonal responses to the antidepressants desipramine and clomipramine, for example, can provide information regarding noradrenergic and serotonergic function, respectively. Pharmacokinetic factors can affect these antidepressant challenge tests. Proper attention to pharmacokinetic issues in the design, implementation, and analysis of data obtained with these probes will provide a more clear understanding of the pharmacodynamic meaning of the results from studies that apply antidepressant challenges.

Antidepressive Agents↗

Acute noradrenergic effects of desipramine in depression.

As a probe of the noradrenergic system in depression, single oral doses of the tricyclic antidepressant desipramine (100 mg) and placebo were administered to unipolar and bipolar depressed patients and healthy volunteers. Plasma concentrations of norepinephrine (NE) were determined 2-3 hours after dosing, with subjects in supine and upright positions. On the placebo day plasma NE was low in a subset of bipolar patients; both groups of depressives demonstrated an exaggerated increase in plasma NE upon standing. After desipramine dosing, the orthostatic procedure resulted in even greater relative increments in plasma NE in both patient groups, with no change in volunteers. These data are consistent with noradrenergic dysregulation in depression.

Administration, Oral↗

The presence of antithyroid antibodies in patients with affective and nonaffective psychiatric disorders.

We determined the frequency of antithyroglobulin and antimicrosomal antibodies in 173 consecutively admitted psychiatric inpatients. (We found antithyroid antibodies in 8% (5/65) of patients with DSM-III major depression, 13% (4/31) with biploar disorder, and in 0% (0/4) of those with schizoaffective disorder.) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole. The overall frequency of positive antithyroid antibody titers in patients with DSM-III affective disorder, 9% (9/99), did not differ from that in patients with nonaffective disorders, 10% (7/68). However, patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients. Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder, even in the absence of lithium exposure. However, as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders, the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation.

Adolescent↗

Statistical analysis of repeated measures in psychiatric research.

We examined the statistical methods applied to research studies that used parallel-groups repeated measures designs. Sixty-three of the 343 articles that were published in four major psychiatry research journals during a 6-month period contained data of this type. Seven (11%) of the 63 articles applied a multivariate analysis of variance. Four (6%) used a univariate analysis of variance with an adjustment for correlated measures. Ten (16%) used a univariate analysis of variance without an adjustment for correlated measures. Twenty (32%) either reduced their repeated measurements to a single value, such as a maximum-change score in each group, or carried out multiple tests at several time points. Twenty-two (35%) of the reports did not provide enough information to allow readers to determine the type of analysis that was applied. We discuss the appropriate selection of analytical techniques for repeated measures designs.

Humans↗

Abnormal neuroendocrine responsivity to acute i.v. clomipramine challenge in depressed patients.

The neuroendocrine responsivity to an acute serotonergic challenge with low-dose i.v. clomipramine was studied in seven drug-free depressed patients and seven age-matched healthy control subjects. The depressed patients had higher baseline prolactin concentrations than the healthy subjects, and their prolactin response to clomipramine, assessed as either the percent of baseline or the log-transformed concentration, was significantly different (delayed and blunted peak response) compared to healthy controls. The growth hormone response was exaggerated in the depressed patients, and there were also trends toward blunting in their cortisol and adrenocorticotropic hormone responses. These results are consistent with previous findings of altered neuroendocrine responses to a variety of putative serotonin agonists in depressed patients.

Adrenocorticotropic Hormone↗