RESUMO
OBJECTIVE: The purpose of this study is to examine whether the reversal of compromised regional cerebral blood flow (rCBF) in older patients with major depressive disorder (MDD) is dependent on specific parameters of selective serotonin reuptake inhibitor (SSRI) treatment and to examine the efficacy of such treatment. METHODS: Forty-five patients with moderate MDD were studied following 8 weeks of treatment with SSRIs. Twelve patients displayed a positive response to SSRIs, whereas 33 patients did not respond to SSRI treatment. A comparison group of 30 healthy volunteers was also studied. The age of all participants was greater than 50 years. Age, gender, and the Hamilton Rating Scale for Depression scores were examined. The rCBF was assessed using 99mTc-ethyl cysteinate dimer single photon emission computed tomography after SSRI treatment. RESULTS: The rCBF levels in the right middle frontal cortex in non-responsive MDD patients were lower compared with responsive MDD patients. Compared with healthy controls, non-responders had significantly lower rCBF levels in the bilateral middle frontal cortex and insula and had significantly higher rCBF levels in the bilateral inferior frontal cortex and left middle temporal cortex. Compared with healthy controls, responders had significantly higher rCBF levels in the left inferior frontal, middle temporal, precentral, and fusiform gyrus. We found no changes in single photon emission computed tomography between pre-treatment and post-treatment stages for the responders to SSRI treatment. CONCLUSION: Hypoperfusion in older, non-responsive MDD patients was primarily localized in the middle frontal cortex. It is possible that the responders to SSRI treatment at baseline already displayed higher rCBF values in the frontal regions.
Assuntos
Antidepressivos/uso terapêutico , Circulação Cerebrovascular/efeitos dos fármacos , Cisteína/análogos & derivados , Transtorno Depressivo Maior/tratamento farmacológico , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Idoso , Idoso de 80 Anos ou mais , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Circulação Cerebrovascular/fisiologia , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: The underlying pathogenic mechanisms and predictors of recurrence in major depressive disorder are still largely unknown. Hypothalamic-pituitary-thyroid (HPT) axis and hypothalamus-pituitary-adrenocortical (HPA) axis dysregulation are thought to be related to the development and course of depression. DESIGN AND SETTING: Over a ten-year period, we investigated whether the results of thyrotropin-releasing hormone (TRH) testing and combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) testing could be correlated with the recurrence of depression in 25 outpatients with clinically remitted major depression for at least 10 years. MATERIALS AND METHODS: Twenty-five patients (16 women and 9 men, 48.1 years of age, SD=11.4, range 22-84) with major depressive disorder were available for evaluation during hospitalization. TRH and DEX/CRH tests were administered at admission. RESULTS: Patients who recurred within ten years after remission exhibited significantly higher thyroid stimulating hormone (TSH) responses to TRH at the time of admission compared to those who did not recur. There was no significant correlation between recurrence and DEX/CRH levels after controlling for age, sex, and body mass index. CONCLUSION: The findings of this study suggest that the TRH test may predict future recurrence in patients with depression.
Assuntos
Transtorno Depressivo/diagnóstico , Sistema Hipotálamo-Hipofisário/fisiopatologia , Testes de Função Adreno-Hipofisária , Sistema Hipófise-Suprarrenal/fisiopatologia , Hormônio Liberador de Tireotropina , Tireotropina/sangue , Hormônio Adrenocorticotrópico/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Hormônio Liberador da Corticotropina , Transtorno Depressivo/sangue , Transtorno Depressivo/fisiopatologia , Dexametasona , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RecidivaRESUMO
BACKGROUND: Two opposing models for the action of ghrelin in the behavioral responses to stress were recently proposed. Some studies suggest that an increase in ghrelin contributes to the mechanisms responsible for the development of stress-induced depression and anxiety, while others suggest that it helps minimize what otherwise would be more severe manifestations of depression and anxiety following stress. METHODS: We measured serum ghrelin levels, Profile of Mood States (POMS) scores and State-Trait Anxiety Inventory scores in nonresponders (treatment-resistant patients; 30) and responders (38) with major depressive disorder (MDD), nonresponders (29) and responders (51) with panic disorder and 97 healthy controls. RESULTS: The ghrelin concentration in nonresponders with MDD was higher than that of responders with MDD and normal controls. The ghrelin concentration in nonresponders with panic disorder was higher than that of normal controls. POMS vigor scores in patients with MDD and panic disorder were significantly decreased compared with those in healthy controls. Other POMS scores in patients with MDD and panic disorder were significantly increased compared with those of healthy controls. Trait and state anxiety of the State-Trait Anxiety Inventory in MDD and panic disorder patients were higher than those in healthy controls. CONCLUSIONS: These results indicate that decreased serum ghrelin levels might be associated with antidepressant treatment to confer the maximum therapeutic effect in patients with MDD and panic disorder.
Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/tratamento farmacológico , Grelina/sangue , Transtorno de Pânico/sangue , Transtorno de Pânico/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Escalas de Graduação PsiquiátricaRESUMO
The effect of renal impairment on the pharmacokinetics of a single oral dose of memantine (10 mg) was determined in Japanese subjects. Subjects were assigned to four groups based on baseline creatinine clearance (CL(CR)): normal renal function (> 80 mL/min, n = 6), and mild (50 to ≤ 80 mL/min, n = 6), moderate (30 to < 50 mL/min, n = 6), and severe renal impairment (5 to < 30 mL/min, n = 7). Mean memantine maximum plasma concentration (C(max)) was similar in the groups (12.66, 17.25, 15.75, and 15.83 ng/mL, respectively), as was mean time to C(max) (6.2, 5.2, 4.3, and 5.4 h, respectively). However, exposure to memantine determined from mean area under the plasma concentration-time curve was 1.62-, 1.97-, and 2.33-times higher in subjects with mild, moderate, and severe renal impairment, respectively, as compared to controls with normal renal function. Mean memantine plasma elimination half-life increased according to increasing renal impairment (61.15, 83.00, 100.13, and 124.31 h, respectively), while mean cumulative urinary recovery of unchanged memantine in 72 h after dosing decreased according to increasing renal impairment (33.68%, 33.47%, 23.60%, and 16.17%, respectively). These results are the same as those in the previous study on caucasian individuals, when compared per body weight. It is suggested that the dose of memantine should be halved in patients with renal impairment.
Assuntos
Antagonistas de Aminoácidos Excitatórios/farmacocinética , Memantina/farmacocinética , Insuficiência Renal/metabolismo , Idoso , Área Sob a Curva , Povo Asiático , Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Antagonistas de Aminoácidos Excitatórios/sangue , Feminino , Humanos , Masculino , Memantina/efeitos adversos , Memantina/sangue , Pessoa de Meia-Idade , População BrancaRESUMO
PURPOSE: To determine the influence of itraconazole on the pharmacokinetics, and the CNS and prolactin-elevating effects of domperidone in humans. METHODS: Fifteen healthy volunteers received either itraconazole (200 mg daily) or placebo for 5 days with a double blind, randomized, cross-over design. A single oral 20-mg dose of domperidone was administered to subjects on day 5. Plasma domperidone and serum prolactin concentrations were measured. The effects of domperidone on CNS were also assessed using self-rating scales and electroencephalography. RESULTS: Itraconazole significantly increased domperidone AUC(0-∞) (3.2-fold) and C(max) (2.7-fold) compared with placebo, but had no significant effect on the elimination half-life of domperidone. The CNS effects of domperidone assessed by self-rating of mood and electroencephalography, and the prolactin-elevating effect, were not significantly affected by itraconazole. A counterclockwise hysteresis was evident in the relationship between plasma domperidone and serum prolactin concentrations. Itraconazole shifted the hysteresis to the right. Concentration-effect modeling procedures yielded a significant linear relationship between hypothetical effect site domperidone concentrations and prolactin levels. Itraconazole reduced the slope of the linear relationship. CONCLUSIONS: Itraconazole significantly increased plasma domperidone concentrations. The interaction is probably mainly due to a reduced first pass elimination by inhibition of CYP3A and/or MDR1. The clinical significance of the altered relationship between domperidone concentrations and prolactin levels caused by itraconazole is still to be determined.
Assuntos
Antifúngicos/administração & dosagem , Domperidona/farmacocinética , Antagonistas de Dopamina/farmacocinética , Itraconazol/administração & dosagem , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Administração Oral , Adulto , Afeto/efeitos dos fármacos , Área Sob a Curva , Biotransformação , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Estudos Cross-Over , Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A , Domperidona/administração & dosagem , Domperidona/sangue , Antagonistas de Dopamina/administração & dosagem , Antagonistas de Dopamina/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Interações Medicamentosas , Eletroencefalografia , Inibidores Enzimáticos/administração & dosagem , Meia-Vida , Humanos , Japão , Modelos Lineares , Masculino , Moduladores de Transporte de Membrana/administração & dosagem , Taxa de Depuração Metabólica , Prolactina/sangue , Autorrelato , Regulação para Cima , Adulto JovemRESUMO
OBJECTIVE: The objective was to determine the effects of the SLCO2B1 c.1457C> T polymorphism and apple juice on the pharmacokinetics of fexofenadine and midazolam in humans. METHODS: Individuals were divided based on the genotype of SLCO2B1 c.1457C> T (n = 14, c.[1457C]+ c.[= ] 5,c.[1457C]+ c.[1457C> T] 5, and c.[1457C> T]+c.[1457C> T] 4). The oral pharmacokinetics of 60 mg fexofenadine and 5mg midazolam were assessed with water or apple juice (1200 ml/day) in a randomized crossover study. OATP2B1-mediated uptake of fexofenadine and midazolam was evaluated with Xenopus laevis oocyte gene-expression system. RESULTS: When fexofenadine was administered with water, subjects with c.[1457C> T] allele showed a significant decrease in fexofenadine in the area under the plasma concentration-time curve (AUC) compared with c.[1457C] + c[= ] subjects (1110 ± 347 vs. 1762 ± 542 ng . h/ml, P< 0.05). When administered with apple juice, a significant decrease in the fexofenadine AUC was observed compared with water (1342 ± 519 vs. 284 ± 79.2 ng . h/ml, P < 0.05). The apple juice induced decrease in fexofenadine AUC was significantly lower in subjects carrying the c.[1457C> T] allele. Neither the genotype nor the apple juice showed significant effects on the pharmacokinetics of midazolam except for a marginally significant decrease in Cmax after administration with apple juice. The uptake of fexofenadine by OATP2B1 cRNA-injected oocytes was significantly higher than that by water-injected oocytes. Apple juice, but not midazolam, significantly decreased the uptake of fexofenadine by OATP2B1 cRNA-injected oocytes. CONCLUSION: The results suggest that fexofenadine is a substrate of OATP2B1, and the transport function of OATP2B1 is subject to the genotype of SLCO2B1 c.1457C> T and apple juice. It is likely that apple juice has little effect on CYP3A.
Assuntos
Bebidas , Malus , Midazolam/farmacocinética , Transportadores de Ânions Orgânicos/genética , Polimorfismo de Nucleotídeo Único/genética , Terfenadina/análogos & derivados , Adulto , Animais , Antialérgicos/administração & dosagem , Antialérgicos/farmacocinética , Área Sob a Curva , Transporte Biológico , Moduladores GABAérgicos/administração & dosagem , Moduladores GABAérgicos/farmacocinética , Humanos , Masculino , Midazolam/administração & dosagem , Terfenadina/administração & dosagem , Terfenadina/sangue , Terfenadina/farmacocinética , Xenopus laevis , Adulto JovemRESUMO
BACKGROUND: Bipolar disorder (BP) is often associated with a change in hypothalamus- pituitary-adrenal axis function change due to chronic stress. Salivary α-amylase (sAA) levels increase in response to psychosocial stress and thus function as a marker of sympathoadrenal medullary system activity. However, sAA has been studied less often than salivary cortisol in BP patients. METHOD: We measured Profile of Mood States and State-Trait Anxiety Inventory scores, heart rate variability, and salivary cortisol levels during electrical stimulation stress in 25 BP patients and 22 healthy volunteers. RESULTS: Tension-anxiety, depression-dejection, anger-hostility, fatigue, and confusion scores in BP patients significantly increased compared with those of the healthy controls. In contrast, the vigor scores of BP patients significantly decreased compared with those of the healthy controls. Significant difference in the sAA levels was observed between BP patients and healthy controls. sAA of female patients was significantly higher than that of female healthy controls, and sAA in male patients tended to be higher than that of male healthy controls. No difference in salivary cortisol was observed between BP patients and the healthy controls. Only three time points were measured before and after the electrical stimulation stress. Furthermore, sAA secretion by BP patients increased before and after electrical stimulation. CONCLUSION: These preliminary results suggest that sAA may be a useful biological marker for BP patients.
RESUMO
Previous studies have reported that the hypothalamic-pituitary-adrenal axis is involved with personality traits. We examined the association between corticotropin-releasing hormone receptor (CRHR) genes and personality traits. We investigated the 12 single-nucleotide polymorphisms of intron CRHR (six in CRHR1 and six in CRHR2, respectively) in 218 healthy volunteers using TaqMan PCR assays. Personality traits were assessed using the Revised NEO-Personality Inventory, the Temperament and Character Inventory, and the State-Trait Anxiety Inventory. No significant associations were observed between CRHR1 and CRHR2 expression and personality traits. These results fail to provide support for an association of CRHR1 and CRHR2 with personality traits in a Japanese adult population.
Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Personalidade/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores de Hormônio Liberador da Corticotropina/genética , Adulto , Povo Asiático/genética , HumanosRESUMO
Salivary α-amylase (sAA) serves as a marker of sympathoadrenal medullary system (SAM) activity. Salivary AA has not been extensively studied in obsessive-compulsive disorder (OCD) patients. In the current study, 45 OCD patients and 75 healthy volunteers were assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Profile of Mood State (POMS), and the State-Trait Anxiety Inventory (STAI). Measures of heart rate variability (HRV), sAA, and salivary cortisol were also obtained following the application of electrical stimulation stress. The Y-BOCS and POMS Tension-Anxiety, Depression-Dejection, Anger-Hostility, Fatigue, and Confusion scores were significantly increased in patients with OCD compared with healthy controls. In contrast, Vigor scores were significantly decreased in patients with OCD relative to scores in healthy controls. There was no difference in HRV between the patients and the controls. Salivary AA levels in female and male OCD patients were significantly elevated relative to controls both before and after electrical stimulation. In contrast, there were no differences in salivary cortisol levels between OCD patients and controls. The elevated secretion of sAA before and after stimulation may suggest an increased responsiveness to novel and uncontrollable situations in patients with OCD. An increase in sAA might be a characteristic change of OCD.
Assuntos
Estimulação Elétrica , Transtorno Obsessivo-Compulsivo/metabolismo , alfa-Amilases Salivares/metabolismo , Adulto , Sintomas Comportamentais/etiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/complicações , Escalas de Graduação Psiquiátrica , Punho/inervaçãoRESUMO
BACKGROUND: Cortisol is an essential hormone in the regulation of the stress response along the HPA axis, and salivary cortisol has been used as a measure of free circulating cortisol levels. Recently, salivary alpha-amylase (sAA) has also emerged as a novel biomarker for psychosocial stress responsiveness within the sympathetic adrenomedullary (SAM) system. PRINCIPAL FINDINGS: We measured sAA and salivary cortisol in healthy volunteers after exposure to the Trier Social Stress Test (TSST) and electric stimulation stress. One hundred forty-nine healthy volunteers participated in this study. All subjects were exposed to both the TSST and electric stimulation stress on separate days. We measured sAA and salivary cortisol levels three times immediately before, immediately after, and 20 min after the stress challenge. The State (STAI-S) and Trait (STAI-T) versions of the Spielberger Anxiety Inventory test and the Profile of Mood State (POMS) tests were administered to participants before the electrical stimulation and TSST protocols. We also measured HF, LF and LF/HF Heart Rate Variability ratio immediately after electrical stimulation and TSST exposure. Following TSST exposure or electrical stimulation, sAA levels displayed a rapid increase and recovery, returning to baseline levels 20 min after the stress challenge. Salivary cortisol responses showed a delayed increase, which remained significantly elevated from baseline levels 20 min after the stress challenge. Analyses revealed no differences between men and women with regard to their sAA response to the challenges (TSST or electric stimulations), while we found significantly higher salivary cortisol responses to the TSST in females. We also found that younger subjects tended to display higher sAA activity. Salivary cortisol levels were significantly correlated with the strength of the applied electrical stimulation. CONCLUSIONS: These preliminary results suggest that the HPA axis (but not the SAM system) may show differential response patterns to distinct kinds of stressors.
Assuntos
Hidrocortisona/metabolismo , Saliva/enzimologia , Estresse Psicológico/enzimologia , alfa-Amilases/metabolismo , Adulto , Ansiedade/enzimologia , Ansiedade/metabolismo , Estimulação Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saliva/metabolismo , Fatores Sexuais , Estatísticas não Paramétricas , Estresse Psicológico/metabolismo , Inquéritos e Questionários , Adulto JovemRESUMO
Psychosocial stress-induced activation of salivary α-amylase (sAA) functions is as a marker of sympathoadrenal medullary system (SAM) activity. However, in contrast to salivary cortisol, sAA has been less extensively studied in panic disorder patients. The present study measured sAA and salivary cortisol levels in patients with panic disorder following electrical stimulation stress. The authors determined Profile of Mood State (POMS) scores and State-Trait anxiety Inventory (STAI) scores, heart rate variability (HRV), and levels of sAA and salivary cortisol in 34 patients with panic disorder and 41 healthy volunteers following the application of electrical stimulation stress. 34 alprazolam-treated patients with panic disorder were divided into non-responder and responder group. Vigor scores in patients with panic disorder were significantly decreased compared with healthy controls. Another score in POMS in patients with panic disorder were significantly increased compared with healthy controls. Trait and state anxiety of STAI in panic disorder patients were higher than healthy controls. There was no difference in either HRV or threshold of electrical stimulation applied between panic disorder patients and healthy controls. SAA levels in the responder group were significantly elevated compared with the non-responder group and controls both before and after electrical stimulation. In addition, there were no differences in salivary cortisol levels between responder and non-responder groups of patients with panic disorder and control. The sample may not be representative of the general population. These preliminary results suggest that sAA might be useful predictive biological markers of treatment responsiveness in patients with panic disorder.