RESUMEN
OBJECTIVE: This study assessed the efficacy of antidepressant treatment (sertraline) and group cognitive behavior therapy, alone or in combination, in primary dysthymia. The clinical features of dysthymia, as well as the functional impairments associated with the illness (e.g., quality of life, stress perception, coping styles), were evaluated. METHOD: Patients (N = 97) diagnosed with primary dysthymia, but no other current comorbid disorder, received either sertraline or placebo in a double-blind design over 12 weeks. In addition, a subgroup of the patients (N = 49) received a structured, weekly group cognitive behavior therapy intervention. RESULTS: Treatment with sertraline, with or without group cognitive behavior therapy, reduced the functional impairment of depression. The reductions were similar in the drug-cognitive therapy group and in subjects who received the drug alone. Furthermore, while group cognitive behavior therapy alone reduced the depression scores, this effect was not significantly greater than the effect of the placebo. The drug treatment also induced pronounced improvement in the functional measures, and in some respects these effects were augmented by group cognitive behavior therapy. Among patients who responded favorably to cognitive behavior therapy, the improvements in the functional measures were similar to those who responded to drug treatment, whereas such functional changes were not seen among patients who responded to placebo. CONCLUSIONS: Sertraline treatment effectively reduces the clinical symptoms and functional impairments associated with dysthymia. Although the group cognitive behavior therapy intervention was less effective in alleviating clinical symptoms, it augmented the effects of sertraline with respect to some functional changes, and in a subgroup of patients it attenuated the functional impairments characteristic of dysthymia.
Asunto(s)
Antidepresivos/uso terapéutico , Terapia Cognitivo-Conductual , Trastorno Distímico/terapia , Psicoterapia de Grupo , Sertralina/uso terapéutico , Adulto , Terapia Combinada , Método Doble Ciego , Trastorno Distímico/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placebos , Resultado del TratamientoRESUMEN
OBJECTIVE: To compare the physiological responses of abused children to different stimuli with responses of children in a reference group and to correlate the physiological responses with intellectual and personality functioning. METHOD: Abused children were compared with a reference group on two batteries of tests that were administered on separate days. In one session, children were shown slides with emotional or cognitive content while heart rate, pulse height, skin conductance, electromyography, and skin temperature were measured. In the other session, intellectual and personality functioning was measured using the WISC-R, Quick Neurological Screening Test, and the Junior Eysenck personality inventory. RESULTS: Abused children had smaller changes in pulse height in the first two stimulus conditions presented ("No Signal" and "Math"), but their electrodermal responses were lower throughout all stimulus conditions. Abused children also had higher introversion and lower Verbal and Full Scale IQ scores. Verbal and Full Scale IQ scores were inversely related to the severity of abuse that had been experienced. When these variables were used in a discriminant function analysis, children were assigned to the correct group 86% of the time. CONCLUSION: These findings support a model that describes the effects of abuse as delaying cognitive development and inhibiting physiological responsiveness to the environment.
Asunto(s)
Nivel de Alerta , Maltrato a los Niños/psicología , Discapacidades del Desarrollo/psicología , Adolescente , Análisis de Varianza , Estudios de Casos y Controles , Niño , Discapacidades del Desarrollo/fisiopatología , Análisis Discriminante , Femenino , Humanos , Masculino , Análisis por ApareamientoRESUMEN
The objective of this study was to determine if the placebo treatment response varied in subgroups of depressed patients (single episode, recurrent, and double depression). Data from placebo-treated patients from seven placebo-controlled clinical trials were pooled and analyzed retrospectively. The placebo response rate was highest for females with a single episode of depression (66.7%) and lowest for females with recurrent depressive episodes (13.3%). Among patients experiencing their first episode, placebo responders had lower Hamilton Rating Scale for Depression (HAMD) total scores at baseline and lower ratings of pschomotor retardation than nonresponders. For patients having a recurrence of an episode, placebo responders had lower baseline ratings of somatic anxiety. The major finding was that patients suffering from their first depressive episode differed from patients with recurrent depressive episodes in the rate of placebo response, effect of gender, and the clinical symptoms that were associated with a positive placebo response.
Asunto(s)
Trastorno Depresivo/tratamiento farmacológico , Efecto Placebo , Antidepresivos/uso terapéutico , Ensayos Clínicos como Asunto , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/psicología , Femenino , Humanos , Masculino , Inventario de Personalidad , Recurrencia , Estudios RetrospectivosRESUMEN
Serotonergic function in 22 patients with primary dysthymia and 22 normal volunteers was evaluated by measuring [3H]serotonin uptake and [3H]paroxetine binding in platelets. A significantly lower maximum rate of serotonin uptake was noted in the dysthymic patients than in the normal subjects, indicating a possible serotonergic dysfunction in dysthymia. However, the values for parameters of paroxetine binding were similar in the two groups.
Asunto(s)
Plaquetas/química , Trastorno Depresivo/sangre , Serotonina/sangre , Adulto , Plaquetas/metabolismo , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Neurológicos , Paroxetina/metabolismo , Receptores de Serotonina/metabolismo , Serotonina/fisiologíaRESUMEN
A subgroup of primary dysthymic patients have been reported to respond to traditional antidepressants and, more recently, to the newer serotonergic agents. Two putative biological markers of affective illness, platelet monoamine oxidase (MAO) activity and plasma cortisol levels following dexamethasone administration, were explored for their diagnostic and predictive potential in dysthymia. Compared to controls, patients had significantly lower platelet MAO activity. Among patients, those that responded to treatment with the serotonergic agent, fluoxetine, had lower pretreatment MAO activity than nonresponders. Higher pretreatment plasma cortisol levels following dexamethasone were also associated with a positive treatment response to this medication. These findings support the view that there is a biological substrate for some subgroups of dysthymics. This biological component may involve the hypothalamic pituitary adrenal axis and serotonergic system(s).
Asunto(s)
Trastorno Depresivo/sangre , Dexametasona , Fluoxetina/uso terapéutico , Hidrocortisona/sangre , Monoaminooxidasa/sangre , Adulto , Edad de Inicio , Análisis de Varianza , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Serotonina/fisiología , Factores SexualesRESUMEN
The present study investigated pre- and post-treatment 24-h urinary metabolites of monoamines and melatonin as a function of response to treatment in primary early onset dysthymic patients. The main finding was that treatment responders had lower urinary 5-hydroxyindoleacetic acid (5-HIAA) levels prior to treatment. Following treatment, urinary 5-HIAA tended to be decreased in nonresponders and increased in responders. As well, metanephrine levels were lower and 6-sulphatoxymelatonin levels were higher in responders prior to treatment. These data support the view that there is a biological substrate for certain subgroups of dysthymia, part of which may involve serotonergic systems.
Asunto(s)
Trastorno Depresivo/orina , Epinefrina/orina , Fluoxetina/uso terapéutico , Melatonina/orina , Norepinefrina/orina , Serotonina/orina , Adulto , Edad de Inicio , Análisis de Varianza , Creatinina/orina , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Valores de Referencia , Resultado del TratamientoRESUMEN
The relationship between plasma and brain amino acids and short-term food intake after administration of albumin, or its constituent amino acids, was examined. Rats given protein (0.85 g chicken egg albumin) or an amino acid mixture patterned after egg albumin reduced their food intake during 1 h of feeding beginning 30 min after gavage. Similarly, when given separately, the essential (EAA) and nonessential amino acid (NEAA) fractions of egg albumin caused comparable decreases in food intake. As the dose increased from 0.5 to 1.5 g the duration of anorexia prolonged to 12 h. Little change occurred in plasma amino acids at 30 and 60 min after albumin at 0.85 g, although many increased by 25-50% at 60 min after 1.5 g. Marked changes in plasma occurred after gavage with the total mixture of constituent free amino acids and after either EAA or NEAA fractions. Brain amino acid concentrations were little affected by albumin and did not show consistent changes after the amino acid treatments. Thus the reductions in food intake after ingestion of albumin or of its constituent amino acids were not predicted from the resulting changes in either plasma or brain concentrations of amino acids.
Asunto(s)
Aminoácidos Esenciales/metabolismo , Aminoácidos/metabolismo , Encéfalo/metabolismo , Proteínas en la Dieta , Conducta Alimentaria , Administración Oral , Aminoácidos/análisis , Aminoácidos/sangre , Aminoácidos Esenciales/administración & dosificación , Análisis de Varianza , Animales , Pollos , Cinética , Masculino , Ovalbúmina/química , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
Pharmacological treatment of dysthymia is a contentious issue mainly because of the traditional view that this disorder has characterological origins and responds to psychotherapy. However, Akiskal's subtyping of primary dysthymia, which was based in part on its response to older antidepressants, can assist in the prediction of responses to antidepressants. Specific serotonin reuptake inhibitors (SSRIs) have equal efficacy but fewer adverse effects and greater tolerability than older antidepressants. Therefore, SSRIs appear to be a viable treatment option for these patients although there are few documented systematic studies of the use of these agents in primary dysthymia. An open study was conducted to determine the efficacy of fluoxetine in primary dysthymia (DSM-III-R and Akiskal's criteria). A good response was observed in the subaffective subtype but not in the character spectrum group. Overall, the antidepressant was tolerated well, with significant adverse effects reported and responders showing reductions in both depressive and anxious symptoms. These initial findings indicate a potential role for SSRIs in the pharmacotherapy of dysthymia.
Asunto(s)
Trastorno Depresivo/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Adulto , Enfermedad Crónica , Trastorno Depresivo/genética , Trastorno Depresivo/psicología , Femenino , Fluoxetina/efectos adversos , Fluoxetina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Inventario de Personalidad , Pronóstico , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Resultado del TratamientoRESUMEN
The role of adrenal hormones in mediating the increase in blood glucose levels following several stressful stimuli (environmental and pharmacological) was studied. The role for brain norepinephrine systems in the initiation of the BG response to these challenges was investigated as well. There is disagreement as to whether stress-induced increases in blood glucose levels are mediated primarily by hormonal or neural stimulation of the liver. A stressful stimulus probably causes increases in blood glucose levels by activating neural connections from the brain to both the liver and the adrenal medulla. The relative contribution that each of these pathways makes to the overall blood glucose response may be dependent on certain factors, such as the type of preparation used (awake or anesthetized, fasted or fed) and the intensity of the stimulus used to induce hyperglycemia. In the experiments reported here, which were performed in awake male rats, we found that increases in blood glucose levels following brief footshock stress, injection of 2-deoxy-D-glucose, exposure to the odor of a predator, and electrical stimulation of the hypothalamus were almost entirely eliminated by removal of the adrenal medullae, a procedure that does not damage hypothalamic norepinephrine systems or the multi-synaptic neural pathways from the hypothalamus to the liver. Furthermore, rather than having impaired blood glucose responses, rats that were depleted of brain norepinephrine showed normal responses to the injection of adrenergic agonists (including epinephrine), and potentiated responses to stressful stimuli compared to non-depleted controls. We conclude that: (1) rapid changes in blood glucose levels that occur following the stressful stimuli used here are mediated mainly by the release of epinephrine from the adrenal medullae and (2) intact brain norepinephrine systems are not required for these increases in blood glucose to occur.
Asunto(s)
Médula Suprarrenal/fisiopatología , Glucemia/metabolismo , Encéfalo/fisiopatología , Hipotálamo/fisiología , Norepinefrina/fisiología , Estrés Fisiológico/metabolismo , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Clonidina/farmacología , Corticosterona/sangre , Desoxiglucosa/farmacología , Estimulación Eléctrica , Isoproterenol/farmacología , Masculino , Norepinefrina/metabolismo , Ratas , Ratas EndogámicasRESUMEN
The effect of phenylalanine (Phe) on plasma and brain Phe and tyrosine (Tyr) levels and on short-term food intake in male rats was measured after intragastric (i.g.), subcutaneous (s.c.) and intraperitoneal (i.p.) administration. Compared to equimolar alanine (Ala), which served as the control, Phe significantly suppressed feeding at a dose of 90 mg/kg body wt when given i.p., but doses up to 720 mg/kg body wt had no effect when given i.g. or s.c. The high doses of Phe given by the i.g. or s.c. route resulted in higher levels of Phe in both plasma and brain than those following i.p. injection (90 mg/kg body wt). Furthermore, brain Tyr levels after i.g. Phe (720 mg/kg body wt) were equal to or higher than after i.p. Phe (90 mg/kg body wt). We conclude that the route of administration is an important variable influencing the effects of Phe on feeding behavior, and that these effects are not readily explained by plasma or brain Phe and Tyr concentrations.
Asunto(s)
Química Encefálica/efectos de los fármacos , Ingestión de Energía/efectos de los fármacos , Fenilalanina/administración & dosificación , Plasma/metabolismo , Alanina/administración & dosificación , Alanina/metabolismo , Alanina/farmacología , Animales , Inyecciones Intraperitoneales , Inyecciones Subcutáneas , Intubación Gastrointestinal , Hígado/metabolismo , Masculino , Fenilalanina/metabolismo , Fenilalanina/farmacología , Ratas , Ratas EndogámicasRESUMEN
1. The purpose of the present experiments was to determine which adrenergic receptor(s) mediated the blood glucose surge following administration of epinephrine and brief footshock stress. 2. It was found that the order of potency of adrenergic agonists to increase blood glucose levels was: clonidine (alpha 2) much greater than epinephrine (alpha + beta) much greater than isoproterenol (beta) greater than phenylephrine (alpha 1). 3. The blood glucose increases caused by both epinephrine and footshock stress were greatly attenuated by the alpha-adrenergic antagonist, phentolamine (1.0 and 5.0 mg/kg ip), while the beta-adrenergic antagonist, propranolol (1.0 or 5.0 mg/kg ip), was without effect. Furthermore, it was found that the alpha 2-adrenergic antagonist, yohimbine (5.0 mg/kg ip), attenuated the epinephrine-induced increase in blood glucose levels, whereas the alpha 1 antagonist, phenoxybenzamine (5.0 mg/kg ip) dramatically potentiated the rise in glucose levels. 4. We conclude that the increase in blood glucose levels following brief footshock stress or injection of epinephrine is mediated by alpha 2-adrenergic receptors.
Asunto(s)
Glucemia/metabolismo , Epinefrina/farmacología , Receptores Adrenérgicos alfa/fisiología , Animales , Clonidina/farmacología , Electrochoque , Isoproterenol/farmacología , Cinética , Masculino , Fenilefrina/farmacología , Ratas , Ratas Endogámicas , Receptores Adrenérgicos alfa/efectos de los fármacosRESUMEN
High affinity [3H]imipramine binding, endogenous levels of serotonin and noradrenaline, and serotonin uptake were determined in brain regions of rats with selective destruction of serotonergic neurons by 5,7-dihydroxytryptamine (5,7-DHT), of adrenergic neurons by 6-hydroxydopamine (6-OHDA), and of rats treated with reserpine. Neonatal treatment with 5,7-DHT resulted in a significant decrease of both serotonin levels and density (Bmax) of high affinity [3H]imipramine binding sites in the hippocampus. In contrast, an elevation of serotonin levels and an increase in Bmax of [3H]imipramine binding were noted in the pons--medulla region. No changes were observed in the noradrenaline content in either of these regions. Intracerebral 6-OHDA lesion produced a drastic suppression of noradrenaline levels in cerebral cortex but failed to alter the binding affinity (KD) or density (Bmax) of [3H]imipramine recognition sites. A single injection of reserpine (2.5 mg/kg) resulted in marked depletion of both serotonin (by 57%) and noradrenaline (by 86%) content and serotonin uptake (by 87%) in the cerebral cortex but had no significant influence of the parameters of high affinity [3H]imipramine binding in this brain region. The results suggest that high affinity [3H]imipramine binding in the brain is directly related to the integrity of serotonergic neurons but not to the magnitude of the uptake or the endogenous levels of the transmitter, and is not affected by damage to noradrenergic neurons or by low levels of noradrenaline.
Asunto(s)
Encéfalo/metabolismo , Proteínas Portadoras , Receptores de Droga , Receptores de Neurotransmisores/metabolismo , Serotonina/metabolismo , 5,7-Dihidroxitriptamina/farmacología , Animales , Animales Recién Nacidos , Hidroxidopaminas/farmacología , Masculino , Norepinefrina/metabolismo , Oxidopamina , Unión Proteica , Ratas , Ratas Endogámicas , Reserpina/farmacología , Simpatectomía QuímicaRESUMEN
Rats that had undergone combined dorsal noradrenergic bundle lesion (DNBL) and bilateral adrenalectomy were impaired in acquiring a conditioned avoidance response when tested 1 week following surgery. Normal acquisition was observed, however, when testing occurred 3 weeks or more after surgery despite low levels of both plasma corticosterone and brain norepinephrine at that time. Furthermore, neither neonatal systemic administration of 6-hydroxy-dopamine to deplete forebrain norepinephrine, combined with the corticosterone inhibitor metyrapone, nor the pharmacological blockade of noradrenergic receptors, combined with adrenalectomy, disrupted acquisition of the avoidance response. Thus, the combination of forebrain norepinephrine loss and low plasma corticosterone does not inevitably impair avoidance acquisition. Rather, the determining factor for such impairment seems to be the interval between surgery and testing. The impairment at 1 week following DNBL and adrenalectomy occurred only for rats tested during the dark phase of their light cycle. In addition, the DNBL abolished the effect of the light/dark cycle on posttraining plasma corticosterone. These results demonstrate the importance of the phase of the rat's diurnal rhythm on both the hormonal and the behavioral effects of altering the pituitary-adrenal axis and/or forebrain norepinephrine. Because adrenocorticotropin, corticosterone, and vasopressin all show diurnal patterns of release, it cannot be determined at this time which, if any, of these hormones is most important for the behavioral results reported here.
Asunto(s)
Corticoesteroides/fisiología , Reacción de Prevención/fisiología , Encéfalo/fisiología , Condicionamiento Clásico/fisiología , Norepinefrina/fisiología , Adrenalectomía , Animales , Corticosterona/sangre , Luz , Masculino , Vías Nerviosas/fisiología , Ratas , Ratas EndogámicasRESUMEN
Three days after the subcutaneous implant of a dexamethasone pellet, which depletes both corticosterone and ACTH, normal rats showed impaired acquisition of a two-way avoidance task. Rats who had received systemic 6-hydroxydopamine at birth to lesion the forebrain noradrenergic terminals from the locus coeruleus did not show this impairment. After a single injection of metyrapone, which inhibits corticosterone synthesis and increases ACTH release, both intact and norepinephrine (NE)-depleted rats showed impaired avoidance acquisition. After the seventh injection, however, acquisition in normal rats was no longer impaired by the drug while the NE-depleted rats were still deficient. These results indicate that the simple combination of forebrain NE loss with reduced corticosterone levels does not necessarily retard avoidance acquisition. Rather, they suggest that the NE efferents from the locus coeruleus are essential for the brain's adaptation to at least some behavioral consequences of changes in the circulating level of ACTH.
Asunto(s)
Dexametasona/farmacología , Hidroxidopaminas/farmacología , Locus Coeruleus/efectos de los fármacos , Metirapona/farmacología , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Hormona Adrenocorticotrópica/sangre , Animales , Animales Recién Nacidos , Reacción de Prevención/efectos de los fármacos , Tronco Encefálico/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Corticosterona/sangre , Femenino , Hipocampo/efectos de los fármacos , Masculino , Vías Nerviosas/efectos de los fármacos , Norepinefrina/metabolismo , Oxidopamina , Embarazo , Ratas , Ratas EndogámicasRESUMEN
The effects of chlordiazepoxide (CDZ) in extinction and punishment-conflict tasks were examined in rats after neonatal systemic administration of 6-hydroxydopamine (6-OHDA) to deplete forebrain norepinephrine (NE). At about 70 days of age the rats were water deprived and trained for three days to drink in a novel apparatus. On the fourth day (test day) drinking was either extinguished by elimination of water from the drinking tube or punished by lick-contingent shock. Just prior to this test session half of the vehicle and half of the 6-OHDA treated rats were given an injection of CDZ (8 mg/kg IP). Both the injection of CDZ and forebrain NE depletion prolonged responding during extinction and reduced the suppressant effects of punishment in male rats, and these effects were of similar magnitude. Furthermore, CDZ was as effective in neonatal 6-OHDA treated male rats as in vehicle treated rats indicating that decreased transmission is ascending NE fibers caused by CDZ is not solely responsible for its behavioral effects in extinction and conflict tasks. Rather, these effects may involve cooperative mediation by both noradrenergic and serotonergic forebrain terminals. Unexpectedly, CDZ's anti-extinction effect was absent in female rats and its anti-conflict effect observed only in NE depleted females.