RESUMO
BACKGROUND: Postpartum depression (PPD) affects approximately 13% of women and has a negative impact on mother and infant, hence reliable biological tests for early detection of PPD are essential. We aimed to identify robust predictive biomarkers for PPD using peripheral blood gene expression profiles in a hypothesis-free genome-wide study in a high-risk, longitudinal cohort. METHOD: We performed a genome-wide association study in a longitudinal discovery cohort comprising 62 women with psychopathology. Gene expression and hormones were measured in the first and third pregnancy trimesters and early postpartum (201 samples). The replication cohort comprised 24 women with third pregnancy trimester gene expression measures. Gene expression was measured on Illumina-Human HT12 v4 microarrays. Plasma estradiol and estriol were measured. Statistical analysis was performed in R. RESULTS: We identified 116 transcripts differentially expressed between the PPD and euthymic women during the third trimester that allowed prediction of PPD with an accuracy of 88% in both discovery and replication cohorts. Within these transcripts, significant enrichment of transcripts implicated that estrogen signaling was observed and such enrichment was also evident when analysing published gene expression data predicting PPD from a non-risk cohort. While plasma estrogen levels were not different across groups, women with PPD displayed an increased sensitivity to estrogen signaling, confirming the previously proposed hypothesis of increased sex-steroid sensitivity as a susceptibility factor for PPD. CONCLUSIONS: These results suggest that PPD can be robustly predicted in currently euthymic women as early as the third trimester and these findings have implications for predictive testing of high-risk women and prevention and treatment for PPD.
Assuntos
Depressão Pós-Parto/diagnóstico , Depressão Pós-Parto/metabolismo , Terceiro Trimestre da Gravidez/metabolismo , Transcriptoma/fisiologia , Adulto , Biomarcadores/metabolismo , Depressão Pós-Parto/sangue , Feminino , Estudo de Associação Genômica Ampla , Humanos , Estudos Longitudinais , Gravidez , Terceiro Trimestre da Gravidez/sangueRESUMO
Thousands of stream miles in the southern Piedmont region are impaired because of high levels of suspended sediment. It is unclear if the source is upland erosion from agricultural sources or bank erosion of historic sediment deposited in the flood plains between 1830 and 1930 when cotton farming was extensive. The objective of this study was to determine the source of high stream suspended sediment concentrations in a typical southern Piedmont watershed using sediment fingerprinting techniques. Twenty-one potential tracers were tested for their ability to discriminate between sources, conservative behavior, and lack of redundancy. Tracer concentrations were determined in potential sediment sources (forests, pastures, row crop fields, stream banks, and unpaved roads and construction sites), and suspended sediment samples collected from the stream and analyzed using mixing models. Results indicated that 137Cs and 15N were the best tracers to discriminate potential sediment sources in this watershed. The delta15N values showed distinct signatures in all the potential suspended sediment sources, and delta15N was a unique tracer to differentiate stream bank soil from upland subsurface soils, such as soil from construction sites, unpaved roads, ditches, and field gullies. Mixing models showed that about 60% of the stream suspended sediment originated from eroding stream banks, 23 to 30% from upland subsoil sources (e.g., construction sites and unpaved roads), and about 10 to 15% from pastures. The results may be applicable to other watersheds in the Piedmont depending on the extent of urbanization occurring in these watersheds. Better understanding of the sources of fine sediment has practical implications on the type of sediment control measures to be adopted. Investment of resources in improving water quality should consider the factors causing stream bank erosion and erosion from unpaved roads and construction sites to water quality impairment.
Assuntos
Monitoramento Ambiental , Sedimentos Geológicos , Rios/química , Movimentos da Água , Agricultura , Conservação dos Recursos Naturais/métodos , Georgia , Árvores , Poluentes da ÁguaRESUMO
The first reliable, securely dated full- and late-glacial pollen stratigraphy from Eastern Beringia forces the rejection of the widely held hypothesis of a steppetundra or grassland associated with extinct vertebrates and early humans. The arctic-alpine fossil flora and low pollen influx suggest a sparse tundra similar to modern herb fell-field vegetation.
RESUMO
Quality control serum samples and postdexamethasone plasma pools were used to compare 16 commercial cortisol radioimmunoassay kits with the competitive protein-binding assay for plasma glucocorticoids that we used to standardize the dexamethasone suppression test (DST). Thirteen radioimmunoassays gave higher criterion values for the DST than those established using the competitive protein-binding assay. The range of radioimmunoassay criterion values was 4.34 to 8.70 mu mg/dL. Possible explanations are given for these findings, and their importance to the clinical utility of the DST are emphasized. Each laboratory should validate its own criterion cortisol value for depression based on local data, including appropriate control groups.
Assuntos
Transtorno Depressivo/diagnóstico , Dexametasona , Hidrocortisona/sangue , Radioimunoensaio/normas , Transtorno Depressivo/sangue , Glucocorticoides/sangue , Humanos , Laboratórios/normas , Ensaio Radioligante/normas , Kit de Reagentes para Diagnóstico/normas , Valores de ReferênciaRESUMO
The effects of the alpha-adrenergic agonist methoxamine on the human hypothalamic-pituitary-adrenal axis was assessed by a placebo-controlled study in the morning and one in the evening. A 5-mg iv bolus dose of methoxamine in normal subjects caused a significant rise in plasma ACTH and cortisol concentrations in the morning study. However, no significant change in plasma cortisol or ACTH concentrations was noted during the evening study. These studies suggest the existence of a diurnal variation in alpha 1-adrenergic regulation of the hypothalamic-pituitary-adrenal axis.
Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Ritmo Circadiano , Hidrocortisona/metabolismo , Receptores Adrenérgicos alfa/fisiologia , Adulto , Humanos , Masculino , Metoxamina/farmacologia , Fatores de TempoRESUMO
BACKGROUND: Pregnancy and the postpartum period are a time of increased risk for women to develop mood disorders. As such, the reproductive safety data on antidepressant use during pregnancy have rapidly expanded over the last decade; however, there is relatively sparse information on maternal/fetal exchange of these medications and no data reporting their concentrations in amniotic fluid. METHODS: We report on three women treated during pregnancy with fluvoxamine, sertraline, and venlafaxine, respectively. Amniotic fluid at amniocentesis and umbilical cord blood and maternal blood at delivery were collected and analyzed for antidepressant concentrations using high performance liquid chromatography with UV detection. RESULTS: Antidepressant and metabolite concentrations were detectable in all amniotic fluid samples, though parent compound concentrations were less than maternal serum and umbilical cord blood concentrations. No adverse effects of the medication were reported. CONCLUSIONS: The presence of these antidepressants in amniotic fluid suggests that fetal exposure to these medications is continual and may occur through a variety of paths, thus accounting for increased fetal exposure. These paths include circulatory via placental passage, gastrointestinal via fetal swallowing, and respiratory secondary to fetal lung absorption.
Assuntos
Líquido Amniótico/química , Antidepressivos/química , Sangue Fetal/química , Adulto , Antidepressivos/farmacocinética , Antidepressivos de Segunda Geração/farmacocinética , Cromatografia Líquida de Alta Pressão , Cicloexanóis/farmacocinética , Feminino , Fluvoxamina/farmacocinética , Humanos , Gravidez , Sertralina/farmacocinética , Espectrofotometria Ultravioleta , Cloridrato de VenlafaxinaRESUMO
BACKGROUND: Despite the widespread study of the dexamethasone suppression test (DST) in patients diagnosed with major depression, it has been less well studied during manic and mixed states of bipolar disorder. METHODS: Cortisol response to the administration of 1 mg of dexamethasone was studied in 44 patients diagnosed bipolar disorder, manic (n = 37) or mixed (n = 7). Dexamethasone levels and cortisol responses were compared between these groups. Four patients initially meeting criteria for bipolar disorder, mixed, and 7 patients initially meeting criteria for bipolar disorder, manic, all of whom were characterized as DST nonsuppressors, were retested after remission. RESULTS: Dexamethasone levels were lower and cortisol levels higher in those patients diagnosed bipolar disorder, mixed. An inverse correlation was found between log-transformed dexamethasone levels and log-transformed cortisol levels at 3 PM (r = -.619, p < or = .001) and 10 PM (r = -.501, p < or = .001). In those subjects retested after remission, dexamethasone levels were higher and cortisol levels lower than during the manic and mixed states. CONCLUSIONS: Disturbances in the hypothalamic-pituitary-adrenal axis are observed frequently during mixed states of bipolar disorder, but are also not uncommon in purely manic episodes. These changes appear to be state dependent and revert with treatment.
Assuntos
Transtorno Bipolar/sangue , Dexametasona/sangue , Hidrocortisona/sangue , Adolescente , Adulto , Idoso , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Dexametasona/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação PsiquiátricaRESUMO
Twenty physically healthy men with schizophrenia responded to a 15-item questionnaire inquiring about their usual and their present (on medications) sexual functioning. Two summary measures of present impairment (the average of items 7-13 that detail the patients' specific complaints of impairment, and item 15, the interviewer's global judgment of impairment) were significantly correlated with each other and with the differences between usual and present reported frequencies of erection and masturbation. More severe impairment on these summary measures was significantly associated with greater biological evidence of dopamine blockade (more severe extrapyramidal side effects and higher serum prolactin levels).
Assuntos
Escalas de Graduação Psiquiátrica , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Comportamento Sexual , Adulto , Doenças dos Gânglios da Base/induzido quimicamente , Doenças dos Gânglios da Base/diagnóstico , Flufenazina/efeitos adversos , Flufenazina/uso terapêutico , Haloperidol/efeitos adversos , Haloperidol/uso terapêutico , Hospitalização , Humanos , Libido/efeitos dos fármacos , Masculino , Masturbação , Ereção Peniana/efeitos dos fármacos , Projetos Piloto , Esquizofrenia/tratamento farmacológico , Comportamento Sexual/efeitos dos fármacos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Variable dexamethasone kinetics is a possible confound in the dexamethasone suppression test. Modifications to include dexamethasone plasma levels and specific dexamethasone "windows" have been proposed. Our study aims to validate our proposed dexamethasone windows in an independent sample of 121 subjects. METHODS: We performed dexamethasone suppression tests in 162 subjects with mixed psychiatric diagnoses. Dexamethasone levels and beta-phase half-life of dexamethasone were computed for suppressors and nonsuppressors. RESULTS: Dexamethasone levels were lower in nonsuppressors than in suppressors. Dexamethasone levels correlated inversely with cortisol levels in the total sample, but were nonsignificant or weakly associated in those samples restricted to the windows. The beta-phase half-life of dexamethasone was shorter in nonsuppressors. The dexamethasone windows were validated at 3:00 PM and 10:00 PM. We propose 4.0 ng/mL as a revised upper limit of the 8:00 AM dexamethasone window. CONCLUSIONS: The plasma dexamethasone level is confirmed as a confound in the dexamethasone suppression test through more rapid dexamethasone clearance in nonsuppressors. Application of dexamethasone windows will reduce this source of test variance.
Assuntos
Dexametasona/farmacocinética , Glucocorticoides/farmacocinética , Transtornos Mentais/diagnóstico , Testes de Função do Córtex Suprarrenal , Adulto , Dexametasona/sangue , Feminino , Glucocorticoides/sangue , Meia-Vida , Humanos , Hidrocortisona/sangue , Masculino , Transtornos Mentais/sangue , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos TestesRESUMO
It is well established that the adrenocorticotropic hormone (ACTH) stimulates the synthesis and release of cortisol from the adrenal cortex, but the role of ACTH in the physiological regulation of basal cortisol secretion has received surprisingly little study. The authors studied the nocturnal and early morning secretory pulses of cortisol and ACTH in normal subjects. A pulse detection algorithm was developed. The relationship between ACTH and cortisol pulses in terms of temporal and proportional relationship is described. Pulse concomitance for ACTH with cortisol was 47% and for cortisol with ACTH pulses it was 60%. The first description of the relationship between concomitant ACTH and cortisol pulse magnitudes in humans is presented. A highly significant linear relationship between the magnitudes of ACTH and cortisol pulses is shown. Putative reasons for dissociated pulses and the potential implication of these findings are discussed.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Ritmo Circadiano/fisiologia , Hidrocortisona/sangue , Adulto , Humanos , Pessoa de Meia-Idade , Radioimunoensaio , Valores de ReferênciaRESUMO
Altered bioavailability or altered pharmacokinetics of dexamethasone (dex) may contribute to a positive Dexamethasone Suppression Test (DST) in psychiatric patients. We measured plasma dex and plasma cortisol concentrations in 32 patients with primary major depressive disorder (MDD), 14 patients with other psychiatric disorders, and 16 normal controls. Cortisol was measured by the competitive protein binding (CPB) assay and dex by RIA (IgG Corp.). Additionally, cortisol was measured by a fluorescent polarization immunoassay (FPIA) available on the Abbott TDx analyzer in an attempt to validate this method for use in the DST. The agreement between FPIA and CPB cortisol results was excellent. Depressed nonsuppressors, by definition, had significantly higher mean plasma cortisol concentrations than depressed suppressors, psychiatric controls, and normal volunteers at 8:00 AM, 3:00 PM, and 10:00 PM postdex. When DST nonsuppressors and suppressors were compared regardless of diagnostic group, plasma dex concentrations were significantly lower (p less than 0.01) in the DST nonsuppressors. There was a significant negative correlation between plasma cortisol levels and plasma dex levels across all subjects at 8:00 AM (r = -0.365, n = 44, p less than 0.05). When the subjects were sorted by diagnostic category, there was a strong, but not statistically significant, trend toward lower plasma dex concentrations in the melancholic nonsuppressors versus the melancholic suppressors and between the psychiatric control non-suppressors and the corresponding suppressor group. These relationships disappeared when we restricted our analyses to an empirically derived middle range of plasma dex concentrations within which the DST results were considered to be valid. We conclude that bioavailability or pharmacokinetics of dex may significantly contribute to DST results. Further investigation is needed to determine whether or not the quantification of dex and its metabolites and their determination at which specific timepoints during the DST will enhance the predictive or interpretive value of the DST in psychiatric patients.
Assuntos
Transtorno Depressivo/sangue , Dexametasona/sangue , Hidrocortisona/sangue , Adulto , Idoso , Análise de Variância , Feminino , Fluorimunoensaio , Humanos , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Esquizofrenia/sangueRESUMO
The role of the metabolites of dexamethasone (DEX) in the dexamethasone suppression test (DST) has never been fully elucidated. We report here our preliminary studies of 6 beta-hydroxydexamethasone (6 OH-Dex), a known metabolite of DEX, on the hypothalamic-pituitary-adrenal (HPA) axis of the rat; its activity in the most commonly used radioimmunoassay for plasma DEX; and its plasma concentrations in a normal human subject during the standard 1.0 mg DST. Six OH-Dex administered subcutaneously to rats at a dose of 1 mg/kg was able to completely suppress corticosterone production for at least 3 hr. In the IgG Corp. radioimmunoassay for plasma DEX, 6 OH-Dex was moderately cross-reactive yielding a 50% cross-reactivity of 10%. Gas chromatographic coupled mass spectroscopic analysis of human plasma samples, obtained 12 to 20 hr after the oral ingestion of 1.0 mg DEX, demonstrated similar plasma concentrations for both the parent compound and the 6-hydroxyl metabolite. The relevance of these findings, particularly to pharmacokinetic studies of the DST, is discussed.
Assuntos
Corticosterona/sangue , Dexametasona/análogos & derivados , Dexametasona/farmacologia , Animais , Dexametasona/farmacocinética , Cromatografia Gasosa-Espectrometria de Massas , Hidrocortisona/sangue , Masculino , Radioimunoensaio , Ratos , Ratos Sprague-DawleyRESUMO
Hyperactivity of the hypothalamus-pituitary-adrenal axis is more common in elderly depression than in younger cohorts and glucocorticoids are known to influence serotonergic systems. The current study explores the interaction of glucocorticoids with aging on serotonin transporter expression and function. Continuous infusions of dexamethasone (26 days) reduced transporter expression in the aged brain but the ability of imipramine to inhibit synaptosomal [3H]serotonin uptake was unimpaired. These effects were unique to aged animals, as prior work with young adults found no effects of dexamethasone on transporter expression. In contrast to the effects in the brain, there were no differences in platelet transporter expression between young and old rats nor did dexamethasone treatment affect the values in the aged group: thus, the platelet may not reliably model these aspects of CNS function. The results suggest that there are basic biologic differences in the effects of glucocorticoids in aged vs. young brain that could contribute to lowered effectiveness to antidepressants in elderly depression; if transport capacity is already reduced by the effects of increased glucocorticoids, further inhibition of transport by antidepressants would have proportionally less impact on synaptic serotonin concentrations.
Assuntos
Envelhecimento/fisiologia , Proteínas de Transporte/fisiologia , Glucocorticoides/fisiologia , Sistema Hipotálamo-Hipofisário/fisiologia , Glicoproteínas de Membrana/fisiologia , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Sistema Hipófise-Suprarrenal/fisiologia , Animais , Antidepressivos Tricíclicos/farmacologia , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Mapeamento Encefálico , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiologia , Dexametasona/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Imipramina/farmacologia , Masculino , Paroxetina/farmacocinética , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Serotonina/sangue , Proteínas da Membrana Plasmática de Transporte de Serotonina , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/fisiologiaRESUMO
Adrenocorticosteroids and serotonergic neurons exert reciprocal regulatory actions, and both are abnormal in depression. We evaluated whether glucocorticoids influence the serotonin transporter in rat platelets and brain by infusing dexamethasone for 26 days, sufficient for replacement of the entire platelet population. Effectiveness was verified by measurement of plasma dexamethasone levels, adrenal atrophy, and growth inhibition. At the end of the infusion, we examined [3H]paroxetine binding to platelet, hippocampal, and cerebrocortical membranes, and [3H]serotonin uptake into platelets and synaptosomes. Dexamethasone slightly reduced platelet [3H]paroxetine binding (12%) and had no effect on binding in brain. Platelet [3H]serotonin uptake was unaffected, but synaptosomal uptake was significantly reduced. In neither platelets nor synaptosomes did dexamethasone alter imipramine's ability to inhibit uptake. Thus, elevated glucocorticoids are not responsible for reduced platelet serotonin transporter expression in depression, nor for resistance to imipramine's effect in platelets in elderly depression; however, reduced synaptosomal [3H]serotonin uptake indicates that glucocorticoids can affect transport efficiency, even when the number of transporter molecules is unaltered.
Assuntos
Proteínas de Transporte/genética , Transtorno Depressivo/fisiopatologia , Modelos Animais de Doenças , Glucocorticoides/fisiologia , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Animais , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Proteínas de Transporte/efeitos dos fármacos , Dexametasona/farmacologia , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/fisiologia , Imipramina/farmacologia , Masculino , Glicoproteínas de Membrana/efeitos dos fármacos , Paroxetina/farmacologia , Ratos , Ratos Sprague-Dawley , Serotonina/fisiologia , Proteínas da Membrana Plasmática de Transporte de SerotoninaRESUMO
To determine whether structural brain abnormalities in patients with depression are related to cortisol state, we examined the relationship between the dexamethasone suppression test (DST) and brain magnetic resonance imaging (MRI) in 40 inpatients with severe depression referred for electroconvulsive therapy (ECT). Prior to ECT, 27 (68%) of the patients exhibited nonsuppression on the DST. Frontal lobe volume was negatively correlated with peak post-dexamethasone cortisone (r = -0.37) and was 13% smaller in DST nonsuppressors than suppressors; these findings were no longer significant after adjustments for age, gender, and cranial size. Lateral and third ventricular volumes were also correlated with peak postdexamethasone cortisol (r = 0.34 and 0.33, respectively), but not after adjustments for age, gender, and cranial size. Subcortical hyperintensity was associated with peak postdexamethasone cortisol and was more common in DST nonsuppressors than suppressors. Again these findings were no longer significant after adjustments for age. Finally, longitudinal DST and brain MRI studies in 11 of these patients revealed no changes in regional brain volumes nor in postdexamethasone cortisol up to six months after ECT. However, within individual patients, postdexamethasone cortisol was positively (and significantly) correlated with frontal lobe volume.
Assuntos
Transtorno Bipolar/diagnóstico , Encéfalo/patologia , Transtorno Depressivo/diagnóstico , Dexametasona , Hidrocortisona/sangue , Imageamento por Ressonância Magnética , Transtornos Neurocognitivos/diagnóstico , Adulto , Transtorno Bipolar/sangue , Transtorno Bipolar/psicologia , Mapeamento Encefálico , Cefalometria , Ventrículos Cerebrais/patologia , Transtorno Depressivo/sangue , Transtorno Depressivo/psicologia , Eletroconvulsoterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/psicologiaRESUMO
To evaluate the hypothalamic-pituitary-adrenal (HPA) axis in patients with posttraumatic stress disorder (PTSD), we measured adrenocorticotropin hormone (ACTH) and cortisol responses following administration of corticotropin-releasing hormone (CRH) in 8 combat veterans with chronic PTSD. The PTSD patients had a significantly lower ACTH response to CRH compared to a control group of normal volunteers. Blunted ACTH responses occurred in patients with PTSD alone, as well as those PTSD patients who also had major depression. The cortisol response, although reduced, was not significantly different from normal. The blunted ACTH response to CRH in PTSD patients is similar to that seen in other psychiatric disorders, such as depression, panic disorder, and anorexia nervosa.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Hormônio Liberador da Corticotropina , Hidrocortisona/sangue , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Adulto , Humanos , Infusões Intravenosas , Masculino , Transtornos de Estresse Pós-Traumáticos/sangueRESUMO
Cortisol and ACTH exhibit circadian rhythmicity, peaking in the early morning. These peaks are associated with increased activity and alertness. We sought to determine whether self-reported daily rhythms predict outcome of a.m. and p.m. CRH challenge in elderly subjects. We surveyed 96 elderly subjects to determine daily rhythms in activity levels, mood, alertness, and performance. Seven healthy subjects were given a cumulative activity score reflecting propensity toward morningness or eveningness. Subjects underwent CRH challenge testing during the morning and evening hours of different days. Baseline plasma ACTH and cortisol concentrations were higher in the morning than in the evening and lower values were associated with lower activity scores (i.e., greater morningness). No trends were apparent between activity score and net hormone response or percent change in hormone concentration.
Assuntos
Ritmo Circadiano/fisiologia , Hormônio Liberador da Corticotropina/farmacologia , Hormônio Adrenocorticotrópico/sangue , Afeto/efeitos dos fármacos , Idoso , Atenção/efeitos dos fármacos , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Atividade Motora/efeitos dos fármacos , Caracteres Sexuais , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: The purpose of this study was to determine the extent of infant medication exposure through breast-feeding during maternal treatment with paroxetine. METHOD: Breast milk and paired maternal and infant sera were collected after 10 days of maternal treatment with paroxetine at a stable daily dose (10-50 mg/day). All samples were analyzed by means of high-performance liquid chromatography with ultraviolet detection and a limit of detection of 2 ng/ml. RESULTS: Breast milk paroxetine concentrations were highly variable (2-101 ng/ml) and were present in all breast milk samples (N=108). A significant gradient effect was observed, with greater paroxetine concentrations found in later portions of breast milk (hind milk) than in early portions (fore milk). No clear time course of paroxetine excretion into breast milk was demonstrated, although maternal paroxetine daily dose reliably predicted both trough and peak breast milk concentrations over a 24-hour period. In 16 mother and infant serum pairs, no detectable concentrations of paroxetine were found in the serum of the nursing infants. CONCLUSIONS: This study extends previous data by demonstrating the presence of paroxetine in the breast milk of nursing women treated with this medication. The low concentrations of paroxetine in infant serum and lack of any observable adverse effects after maternal use of this medication while breast-feeding parallels the available data on other selective serotonin reuptake inhibitors.
Assuntos
Aleitamento Materno , Transtorno Depressivo/tratamento farmacológico , Recém-Nascido/sangue , Leite Humano/química , Paroxetina/análise , Paroxetina/uso terapêutico , Cromatografia Líquida de Alta Pressão , Transtorno Depressivo/metabolismo , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Paroxetina/farmacocinética , Gravidez , Transtornos Puerperais/tratamento farmacológico , Transtornos Puerperais/metabolismoRESUMO
The authors administered the growth hormone-releasing factor (GRF) stimulation test to 19 patients with major depression and 19 age- and sex-matched control subjects to test the hypothesis that a blunted growth hormone (GH) response to clonidine reflects a central alpha 2-adrenergic receptor subsensitivity in depression. GH response to GRF was significantly higher in patients with depression than in control subjects. This group difference was mainly attributable to three of the 19 depressed patients who exhibited markedly high GH responses to GRF. These results suggest that the blunted GH response to clonidine seen in patients with depression is not due to a pituitary defect in GH secretion.
Assuntos
Transtorno Depressivo/diagnóstico , Hormônio Liberador de Hormônio do Crescimento , Hormônio do Crescimento/sangue , Adulto , Fatores Etários , Peso Corporal , Clonidina/farmacologia , Transtorno Depressivo/sangue , Dextroanfetamina/farmacologia , Feminino , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Humanos , Masculino , Receptores Adrenérgicos alfa/efeitos dos fármacosRESUMO
Rats from the Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL), which have been bred for differences in sensitivity to cholinergic agonists, were killed by decapitation under quiet, nonstressful conditions and the concentrations of corticotropin-releasing factor (CRF) in various brain regions, the concentrations of CRF receptors in the anterior pituitary, and plasma ACTH and corticosterone concentrations were determined. A first study revealed that the cholinergically hypersensitive FSL rats exhibited lower concentrations of CRF in the median eminence, locus ceruleus, and prefrontal cortex, but no such changes in some 13 other brain regions. In this first study, the FSL rats had significantly lower plasma ACTH concentrations. However, there were no differences in plasma corticosterone concentrations between the two groups. A second study confirmed the results of the first study and revealed that the density of anterior pituitary CRF receptor binding sites was elevated in the FSL rats. The observed pattern of alterations in these measures of HPA axis activity suggest that the cholinergically supersensitive FSL rats may possess diminished HPA activity.