Biomedical subjects

S E Hendricks

Publications and source records attributed to S E Hendricks.

At least 19 recordsLinked to original sources

PubMed2004

Clinical response augments NK cell activity independent of treatment modality: a randomized double-blind placebo controlled antidepressant trial.

BACKGROUND: Major depressive disorder (MDD) has been associated with alterations in immune function. Suppression of natural killer (NK) cell activity (NKCA) reliably characterizes immunological alterations observed in MDD. Antidepressant pharmacotherapy has been associated with modulation of NKCA. Previous investigations into antidepressant modulation of NKCA have not employed randomized double-blind placebo controlled designs. Thus, it is unknown whether treatment-associated changes in immune function are due to drug, placebo, or spontaneous remission effects. The present investigation examined the effect of antidepressant treatment on NKCA utilizing a randomized double-blind placebo controlled experimental design. METHOD: Patients (N = 16) met DSM-IV criteria for MDD and were randomly assigned to drug (N = 8; citalopram, 20 mg/day) or placebo (N = 8) under double-blind conditions. Severity and pattern of depressive symptoms were assessed by the Hamilton Depression Rating Scale (HDRS). NK cell function was measured using a standard chromium-release assay and NK cell number assessed by flow cytometry. HDRS scores, NK cell function, and NK cell numbers were collected at 0, 1, 2 and 4 weeks of treatment. RESULTS: Clinical response was associated with augmented NKCA independent of treatment condition. Failure to respond to treatment resulted in significantly reduced NKCA over treatment interval. CONCLUSIONS: The present results suggest that alterations in the depressive syndrome, regardless of therapeutic modality, may be sufficient to modulate NKCA during antidepressant trials and thus may significantly impact on co-morbid health outcomes in MDD.

Adult↗

PubMed2001

Monocyte 5-HT1A receptors mediate pindobind suppression of natural killer cell activity: modulation by catalase.

Serotonin (5-hydroxytryptamine; 5-HT) modulates constituents of the immune system. 5-HT1A receptor antagonists potently suppress lymphocyte function. NK cell activity (NKCA) was measured after exposure of mononuclear cells to the 5-HT1A receptor antagonist pindobind and the 5-HT(1C/2) receptor antagonist ketanserin. Elutriated monocytes were exposed to pindobind, incubated with peripheral blood lymphocytes (PBL) in the presence or absence of an H2O2 scavenger catalase, and NKCA measured. Pindobind, but not ketanserin, suppressed NKCA in vitro. Pindobind-treated monocytes suppressed NKCA, whereas pindobind treatment of PBL did not affect NKCA. Catalase inhibited pindobind-induced suppression of NKCA. These data are consistent with previous results that 5-HT modulates NKCA via 5-HT1A receptors on monocytes and suggest that 5-HT may abrogate monocyte suppression of NKCA by inhibiting monocyte signals such as H2O2.

Catalase↗

PubMed2001

Levels of monocyte reactive oxygen species are associated with reduced natural killer cell activity in major depressive disorder.

Major depressive disorder (MDD) is associated with reductions in natural killer cell activity (NKCA), however the mechanism(s) mediating reduced NKCA in MDD has yet to be determined. In light of evidence that MDD is associated with an inflammatory immune response, we propose that reactive oxygen species (ROS), generated by inflammatory leukocytes (monocytes and/or neutrophils), may mediate the suppression of NKCA in MDD. Intracellular levels of monocyte ROS were significantly associated with reductions in NKCA in outpatients (n = 15) diagnosed with MDD. Sleep disturbance was also significantly correlated with reductions in NKCA. Elevated levels of ROS may be an additional characteristic of a subset of depressed patients in whom an inflammatory response persists and elevations in ROS may, in part, mediate the associations observed between MDD, cardiovascular disease, and cancer.

Adult↗

PubMed2000

Multiple ejaculations and chronic fluoxetine: effects on male rat copulatory behavior.

Male rats were treated with fluoxetine (FLX) or vehicle daily for 14 days and copulatory behavior tested on day 15. Rats were either mated to three ejaculations or to sexual exhaustion. Both standard measures and the mount bout analysis were used to evaluate the effects of the chronic FLX on male rat copulatory behavior. Only 56.25% of the animals treated with FLX achieved three ejaculations. FLX inhibited the consumatory aspect of male sexual behavior, especially the ability to achieve three ejaculations, but there was no effect on the propensity of the male to pursue the female. These differences were observed for the first three ejaculations. Analysis of the last three ejaculations in those animals that mated to exhaustion did not reveal an effect of FLX. The behavioral pattern of FLX-treated animals during the first three ejaculations resembled that observed during the last three ejaculatory series in the vehicle-treated animals that mated to exhaustion. The results are discussed in terms of the serotonergic effects on male rat sexual behavior.

Animals↗

PubMed2000

The effects of St. John's Wort (Hypericum perforatum) on NK cell activity in vitro.

St. John's Wort (Hypericum perforatum; H. perforatum) is a popular herbal supplement used to treat mild to moderate depression. H. perforatum possesses serotonergic properties such as inhibition of serotonin (5-hydroxytryptamine; 5-HT) reuptake. Serotonergic pharmacotherapy is associated with amelioration of depression as well as increases in natural killer (NK) cell activity (NKCA). Also, 5-HT and 5-HT analogs augment NKCA in vitro. Considering the serotonergic properties of H. perforatum, the effects of H. perforatum on NKCA were assessed in vitro. Mononuclear cells (MNCs) from normal donors were exposed in vitro to an extract of H. perforatum (LI160s) or established 5-HT stimulators of NKCA. After an overnight incubation, cells were washed and a standard 51Cr-release cytotoxicity assay performed to assess NKCA. LI160s at all concentrations failed to augment NKCA. However, in corroboration of previous studies, 5-HT, the selective serotonin reuptake inhibitors (SSRIs), paroxetine and norfluoxetine, and alpha-interferon augmented NKCA above control levels. Though an efficacious treatment for mild to moderate depression, H. perforatum differs from commonly prescribed serotonergic antidepressants insofar as H. perforatum fails to enhance NKCA in vitro. Therefore, the present results are consistent with pharmacologic studies indicating that H. perforatum possesses, at best, weak serotonergic activity.

Adult↗

PubMed2000

Weekly dosing of fluoxetine for the continuation phase of treatment of major depression: results of a placebo-controlled, randomized clinical trial.

Fluoxetine (FLX) has a unique pharmacokinetic profile. Its major metabolite, norfluoxetine (NFLX), possesses FLX's antidepressant efficacy and a half-life of 7 to 15 days, suggesting the possibility of nonstandard dosing strategies. This study examined the tolerability of a weekly dose and its equivalence to daily dosing of FLX for the continuation phase of treatment for major depressive disorder (MDD). One hundred fourteen subjects initially received open-label treatment with 20 mg of FLX daily for 7 weeks. Subsequently, 70 subjects with a score on the Hamilton Rating Scale for Depression (HAM-D) of 12 or less were randomly assigned in a double-blind design to one of three treatment groups: 20 mg FLX daily (N = 21), 60 mg FLX weekly (N = 28), or placebo (N = 21) and were followed for 7 weeks. HAM-D scores and blood levels of FLX and NFLX were analyzed using a repeated-measures analysis of variance. During the double-blind phase, blood levels for both FLX and NFLX differed across the treatment groups, yet no statistically significant difference in HAM-D scores was observed. There was no difference in the dropout rate across the groups. Subjects could not correctly identify the treatment group into which they were assigned. Weekly dosing of FLX seems to be well tolerated and possibly as effective as daily dosing in maintaining the therapeutic response in subjects with MDD.

Adult↗

PubMed1999

Androgen threshold to activate copulation differs in male rats prenatally exposed to alcohol, stress, or both factors.

Few male rats prenatally exposed to a combination of alcohol and stress copulate spontaneously. This study determined adult sensitivity to testosterone (T) in males prenatally exposed to alcohol, to stress, or to both factors. Sexually naive males were tested with receptive females following castration and implantation of 20-, 30-, or 45-mm Silastic T-filled capsules. Serum T levels provided by these implants were measured. The behavior shown by males exposed only to prenatal alcohol did not differ from untreated control animals at any T dosage. Prenatal stress alone diminished the copulatory potential below control levels only when the intermediate T dosage was provided. Few males exposed to both alcohol and stress copulated under the lowest or the intermediate dose of adult T replacement, but most ejaculated normally when the largest capsule was implanted. The threshold to the sexual behavior-activating-properties of adult T exposure was moderately raised by prenatal stress but was severely affected when prenatal stress was combined with alcohol. We conclude that a diminished sensitivity to androgen in adulthood underlies some copulatory deficits resulting from treatments that alter fetal T levels. Such deficits may be concealed when behavior is evaluated in gonadally intact animals.

Androgens↗

PubMed1999

Antidepressants augment natural killer cell activity: in vivo and in vitro.

Depressed mood has been associated with reduced natural killer cell activity (NKCA). Further, amelioration of depressive symptoms by pharmacotherapy has resulted in augmented NKCA. Serotonin, an indoleamine implicated in the pathophysiology of affective disorders, enhances NKCA in vitro and lymphocytes possess serotonin transporters and receptors. The present study evaluated NKCA in depressed outpatients before and during treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac(R)). Further, the SSRIs, fluoxetine and paroxetine (Paxil(R)), were also incubated in vitro with lymphoid cells to evaluate possible direct effects of SSRIs on NKCA. Depressed outpatients were administered fluoxetine (20 mg/day) for 4 weeks. NKCA and severity of depression were evaluated at weeks 0, 1, 2, and 4. Serum concentrations of fluoxetine and norfluoxetine were obtained as well. Mononuclear cells obtained from nonpatient volunteers were incubated with pharmacologic concentrations of fluoxetine or paroxetine and NKCA measured with a standard chromium release assay. Fluoxetine treatment resulted in decreased symptoms of depression and increased serum concentrations of fluoxetine and norfluoxetine. Further, fluoxetine treatment was associated with augmented NKCA in a subgroup of depressed outpatients exhibiting low NKCA at baseline. Fluoxetine had no effect on NKCA in depressed individuals exhibiting high NKCA at baseline. Incubation of mononuclear cells with fluoxetine and paroxetine augmented NKCA in vitro. The enhancing effects of antidepressants on NKCA in vivo and in vitro indicate a possible direct drug interaction with lymphoid cells during pharmacotherapy, suggesting that pharmacologic treatment of depression may result in enhanced immune competence as indexed by enhanced NKCA and that NKCA could be pharmacologically augmented with antidepressants in individuals with compromised immune function.

Adult↗

PubMed1996

Organizational-activational concept revisited: sexual differentiation in an atherinomorph teleost.

Because of its numerous sexually dimorphic characters, the Western mosquitofish Gambusia affinis affinis is an excellent vertebrate system for addressing questions concerning sexual differentiation. In this review, the actions and limits of gonadal sex steroids, specifically testosterone, on the development of the sexually dimorphic anal fin and its axial and appendicular support are described. Data from our laboratory show that the critical period in this species for the anterior transposition of the male anal fin and its appendicular support occurs during the late embryonic period and that this differentiation of the male phenotypic genital areaduring the critical period is regulated by androgen.

Animals↗

PubMed1996

Modification of CAPS-1 for diagnosis of PTSD in Afghan refugees.

A DSM-III-R based instrument for the assessment of posttraumatic stress disorder (PTSD), the Clinician-Administered PTSD Scale (CAPS-1), was modified to accommodate cultural differences and translated into the Afghan languages Pushto and Farsi (Dari) and administered to 30 Afghan refugees living in the United States. The modified CAPS-1 was found to be practical and reliable. Inter-item correlations were calculated on the frequency and intensity scores for the 17 cardinal symptoms and the eight associated features items of the modified CAPS-1. The four reexperiencing items demonstrated significant independence from the avoidance and arousal symptom clusters. However, the avoidance and arousal symptom clusters were not found to be independent cardinal components of PTSD in our participants. The CAPS-1 criteria for diagnosis of PTSD were met by 50% of the subjects evaluated.

Adolescent↗

PubMed1996

Conditioned taste aversion induced by fluoxetine.

The present study assessed the ability of the serotonin reuptake inhibitor fluoxetine (FLX) and lithium chloride (LiCl) to induce conditioned taste aversion (CTA) to a novel 20% sucrose solution. FLX (2, 5, or 8 mg/kg) or LiCl (10 mg/kg) was administered 30 min after an initial exposure to the solution. A single-bottle test of CTA 24 h after the initial exposure indicated that rats that received FLX, at any dose, or LiCl consumed significantly less solution than did those that received a vehicle treatment following the initial exposure. To examine the possibility that decreased consumption during the CTA test exposure was associated with lasting hypophagia and/or hypodipsia induced by FLX, separate groups of rats, without any prior exposure to the solution, were administered FLX (2, 5, or 8 mg/kg) and given access 24 h later to a 20% sucrose solution. FLX failed to suppress consumption of the solution at any dose. These data suggest that FLX induces an aversive drug state in rats, similar to that induced by LiCl, which serves as a potent conditioned stimulus in CTA. In addition, this CTA is independent of FLX-induced hypophagia and/or hypodipsia. The relevance of these results to the study of hypophagia induced by FLX administration is discussed.

Animals↗

PubMed1996

Prenatal alcohol and stress interact to attenuate ejaculatory behavior, but not serum testosterone or LH in adult male rats.

Restraint stress reduced blood alcohol levels in pregnant rats given a liquid alcohol diet. The male offspring prenatally exposed to both stress and alcohol failed to ejaculate spontaneously, although they copulated normally following exogenous testosterone (T) administration. Males prenatally exposed only to alcohol or only to stress showed no behavioral deficits. Adult serum T and luteinizing hormone levels were normal in both of the fetal alcohol exposed male groups. It appears that the androgen threshold for ejaculatory behavior is elevated in males prenatally exposed to alcohol plus stress and cannot be realized with normal testosterone titers, but it can be attained with exogenous hormone administration. Presumably the alcohol and stress combination interfered with ontogenetic patterns of T needed to fully masculinize the fetal nervous system.

Animals↗

PubMed1996

Fluoxetine and norfluoxetine serum concentrations and clinical response in weekly versus daily dosing.

This study explored serum concentrations of fluoxetine and norfluoxetine in subjects treated under different dosing regimens. Using a placebo-controlled, randomized, double-blind design, we compared 20 mg fluoxetine daily, 60 mg fluoxetine weekly, and a placebo. All subjects had responded positively to a 7-week open-label trial of 20 mg fluoxetine daily. Consistent with numerous attempts to correlate fluoxetine and norfluoxetine blood levels to clinical response, we found no significant relationships between serum concentrations and Hamilton Rating Scale for Depression (HAM-D) scores. Serum concentrations were significantly different among the three treatment groups. Pairing the fact that the serum concentrations of subjects given 60 mg fluoxetine weekly were significantly lower than those given 20 mg daily with the finding that the 60 mg weekly group had lower HAM-D scores suggests that, for stabilized subjects, this nontraditional dosing strategy is at least as effective in treating depression as the standard 20 mg fluoxetine daily treatment.

Adult↗

PubMed1995

Monoaminergic influences on temporal patterning of sexual behavior in male rats.

We evaluated the effects of the serotonin (5-HT) presynaptic uptake blocker fluoxetine (FLX) and the dopamine (DA)/noradrenaline (NE) releaser amantadine (AMA), separately and in combination, on the temporal patterning of male rat sexual behavior. FLX alone increased intermount-bout intervals, time-outs, grooming time, ejaculation latency, number of mounts per mount bout, and number of mount bouts per ejaculation. AMA alone had the opposite effect on these measures. Additionally, AMA, when given in combination with FLX, completely reversed the FLX-induced deficits in copulatory behavior. We interpret our results as suggesting an interaction between 5-HT and catecholamines in the temporal patterning of male rat copulatory behavior.

Amantadine↗

PubMed1995

Amplitude/intensity functions of auditory event-related potentials predict responsiveness to bupropion in major depressive disorder.

Patients diagnosed with major depressive disorder (MDD) and enrolled in an open-label safety surveillance study of a sustained release formulation of bupropion hydrochloride (100 to 300 mg/day) were evaluated with the Hamilton Rating Scale for Depression (HAM-D) immediately before and 6 to 12 weeks after the initiation of drug treatment. Auditory event-related potentials (ERPs) recorded under a stimulus intensity modulation paradigm were also obtained at these times. Patients were classified as responders and nonresponders based on post-treatment HAM-D scores, with responders having HAM-D scores less than 10 and nonresponders having scores greater than 10. Consistent with our previous findings, responders exhibited significantly larger positive slope coefficients for P2 ERP component amplitudes as a function of auditory stimulus intensity obtained at baseline and were not affected by bupropion treatment. Thus, these results further support our previous finding that ERP amplitude/intensity functions measured under a stimulus intensity modulation paradigm provide information about the likelihood of a positive therapeutic response to antidepressant pharmacotherapy in patients with MDD and extends these results to bupropion, a pharmacologically atypical antidepressant agent.

Adult↗

PubMed1994

Fluoxetine-induced inhibition of male rat copulatory behavior: modification by lesions of the nucleus paragigantocellularis.

In Experiment 1, the 5-HT uptake blocker fluoxetine (FLX; 20 mg/kg) reduced the proportion of sexually experienced male rats displaying ejaculations. Among those animals that did ejaculate there was an increase in intromission frequency (IF), ejaculation latency (EL), and postejaculatory interval (PEI) and a reduction in copulatory efficiency (CE) during the final copulatory sequence prior to sexual exhaustion. In Experiment 2, we found similar inhibitory effects of FLX as well as facilitating effects of lesions of the nucleus paragigantocellularis (PGi) on male rat copulatory behavior. Males with PGi lesions displayed more ejaculations and a longer latency to sexual exhaustion compared to intact animals. When FLX was given to rats with PGi lesions, it did not influence the proportion of rats ejaculating nor did it alter IF, EL, or PEI during the final copulatory series prior to exhaustion. These findings suggest that the inhibitory influences of FLX on male rat copulatory behavior are mediated in part by the interaction of FLX with neurons originating in the PGi.

Animals↗

PubMed1994

Event-related potential amplitude/intensity slopes predict response to antidepressants.

We measured event-related potential (ERP) component amplitudes to four intensities of randomly presented tones. Patients diagnosed with major depressive disorder were tested prior to and following a clinical trial of antidepressant medication. Slope of P2 amplitude as a function of stimulus intensity was calculated for each subject and condition. Subjects were divided into two groups (responders and nonresponders) based on their Hamilton Rating Scale for depression scores following treatment. Responders had significantly larger P2 slopes prior to treatment than did nonresponders. P2 slopes did not differ significantly between responders and nonresponders following antidepressant treatment. These data support the conclusion that P2 amplitude/intensity slope may be a predictor of response to treatment with antidepressant medication.

Acoustic Stimulation↗

PubMed1994

Development of the anal fin appendicular support in the western mosquitofish, Gambusia affinis affinis (Baird and Girard, 1854): a reinvestigation and reinterpretation.

Development of the sexually dimorphic anal fin appendicular support of an internal fertilizing bony fish Gambusia affinis affinis was investigated by staining whole-mounted embryos, immature, and adult female and male G. a. affinis with alizarin red S and alcian blue. The tissue was examined histologically to assess development of the amphicelous centrum and to verify specificity of the stains. Our data confirm earlier claims about the development of the male and female characteristics in this species, and we provide for the first time direct embryonic evidence suggesting that development of the sexually dimorphic anal fin appendicular support is biphasic: (1) anteriorization of the most anterior caudal segments, and (2) growth and elongation of hemal arches of vertebrae 14-16. The first process involves a sequential homeotic transformation of hemal arches of vertebrae 11-13 through resorption of mineralized connective tissue, thus forming parapophyses that bear pleural ribs. This process begins in undifferentiated embryos and proceeds similarly in postnatal males and females. During the same period, the second process, likely induced by male gonadal hormones, causes the addition of mineralized connective tissue at the hemal arches of vertebrae 14-16. This second process, which occurs only in males, elongates the hemal arches of vertebrae 14-16 anteriorly. This elongation apparently translocates the anal fin appendicular support (including parts of the hemal spine of the hemal arch of vertebra 13) to the level of vertebra 11. It appears that the developmental programs of both female and male G. a. affinis create an area of 6 vertebrae which are markedly different from any vertebrae anterior to 11 and posterior to 16. We propose to term the area including these vertebrae and the associated anal fin, the genital area. We also propose that the first process, homeotic transformation of caudal into precaudal segments, is regulated by differential expression of control genes, such as homeobox genes, whereas the second process is regulated by gene expression under the control of male gonadal hormones. Conflicting data in the literature can be resolved with this model. Appropriate tests of the model are proposed.

Animals↗