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Biomedical subjects

D B Jarrett

Publications and source records attributed to D B Jarrett.

At least 19 recordsLinked to original sources
PubMed1997

Influence of imipramine on the hypothalamic/pituitary/thyroid axis of the rat.

The effects of the tricyclic antidepressant drug imipramine at different levels of the hypothalamic/pituitary/thyroid axis were investigated in the rat. Intraperitoneal (IP) treatment for 14 days with imipramine at 10 mg/kg, but not 2 mg/kg, reduced serum total thyroxine (T4) and triiodothyronine (T3). A similar decrease in serum total T4 was observed in thyroidectomized T4-treated rats, suggesting that imipramine treatment enhances T4 clearance instead of reducing T4 secretion. There were no parallel decreases in serum free T4 and T3 concentrations, due to the simultaneous increase in the free fractions of both T4 and T3 following imipramine treatment. In vitro experiments using equilibrium dialysis indicated that neither imipramine nor its metabolite desipramine directly influenced the binding of T4 or T3 to their transport proteins following addition to normal serum, suggesting an indirect effect of imipramine or desipramine on free hormone concentrations in vivo. Concentrations of T4 and T3 in the brain, liver, and heart were unaffected by imipramine treatment, suggesting that the drug did not affect cellular uptake and metabolism of T4 and T3. Serum concentrations of thyrotropin (TSH) were unaffected by imipramine pretreatment at either dose level, compatible with the fact that serum free T4 and T3 concentrations were not reduced. Moreover, there was no difference in thyrotrope responsiveness to stimulation by TSH-releasing hormone (TRH) and to inhibition by T4 and T3 in rat anterior pituitary cells cultured ex vivo for 18 hours from control and imipramine-treated rats. Furthermore, in vitro exposure of cultured rat anterior pituitary cells to imipramine and desipramine indicated that both agents decreased TSH secretion only at concentrations greater than 10(-6) mol/L. These concentrations of imipramine and desipramine in the culture medium would exceed the free concentrations of these drugs seen in vivo therapeutically. In addition, no direct effects of 10(-6) mol/L imipramine or desipramine on the TSH response to TRH or to T3 were observed in vitro in cultured pituitary cells. A potential indirect effect of imipramine or desipramine on TSH secretion via altered hypothalamic control of thyrotropes does not seem likely, due to the lack of effect of imipramine treatment on serum TSH concentrations in imipramine-treated rats. In conclusion, imipramine treatment reduces serum total T4 and T3 in the rat, with enhanced clearance being the most likely explanation for the effect on T4. There was no evidence for altered tissue T4 or T3 concentrations or for altered thyrotrope function. The enhanced T4 clearance may explain the reduction in total T4 reported for imipramine-treated depressed patients. However, the effects of imipramine treatment on the transport of thyroid hormones in plasma need to be examined in more detail in patients, since interspecies differences in the nature of the transport proteins preclude extrapolation of the present results from the rat.

Animals↗
PubMed1997

Circadian rhythms in human performance and mood under constant conditions.

UNLABELLED: This study explored the relationship between circadian performance rhythms and rhythms in rectal temperature, plasma cortisol, plasma melatonin, subjective alertness and well-being. Seventeen healthy young adults were studied under 36 h of 'unmasking' conditions (constant wakeful bedrest, temporal isolation, homogenized 'meals') during which rectal temperatures were measured every minute, and plasma cortisol and plasma melatonin measured every 20 min. Hourly subjective ratings of global vigour (alertness) and affect (well-being) were obtained followed by one of two performance batteries. On odd-numbered hours performance (speed and accuracy) of serial search, verbal reasoning and manual dexterity tasks was assessed. On even-numbered hours, performance (% hits, response speed) was measured at a 25-30 min visual vigilance task. Performance of all tasks (except search accuracy) showed a significant time of day variation usually with a nocturnal trough close to the trough in rectal temperature. Performance rhythms appeared not to reliably differ with working memory load. Within subjects, predominantly positive correlations emerged between good performance and higher temperatures and better subjective alertness; predominantly negative correlations between good performance and higher plasma levels of cortisol and melatonin. Temperature and cortisol rhythms correlated with slightly more performance measures (5/7) than did melatonin rhythms (4/7). Global vigour correlated about as well with performance (5/7) as did temperature, and considerably better than global affect (1/7). IN CONCLUSION: (1) between-task heterogeneity in circadian performance rhythms appeared to be absent when the sleep/wake cycle was suspended; (2) temperature (positively), cortisol and melatonin (negatively) appeared equally good as circadian correlates of performance, and (3) subjective alertness correlated with performance rhythms as well as (but not better than) body temperature, suggesting that performance rhythms were not directly mediated by rhythms in subjective alertness.

Adult↗
PubMed1996

Hypothalamic-pituitary-adrenocortical activity and response to cognitive behavior therapy in unmedicated, hospitalized depressed patients.

OBJECTIVE: Surprisingly little research supports the hypothesis that depressions characterized by objective measures of neurobiological dysregulation respond poorly to psychotherapy. Moreover, relevant studies testing this hypothesis have been compromised by low rates of neurobiological abnormality in outpatient samples. The authors therefore investigated response to cognitive behavior therapy in relation to pretreatment measures of hypothalamic-pituitary-adrenocortical (HPA) activity in hospitalized, yet unmedicated, patients. METHOD: The subjects were 29 unmedicated, hospitalized patients with major depression (DSM-III-R and Schedule for Affective Disorders and Schizophrenia/Research Diagnostic Criteria), nonpsychotic/nonbipolar subtype. After a 7- to 14-day evaluation, urinary free cortisol levels and dexamethasone suppression tests (DSTs) were obtained. Patients were treated for an average of 3 weeks with intensive individual cognitive behavior therapy. Response was assessed in relation to clinical severity of illness and pretreatment HPA parameters. RESULTS: Response to inpatient cognitive behavior therapy was inversely associated with pretreatment urinary free cortisol concentrations, although not strongly correlated with DST results. Overall, 12 (92%) of 13 cortisol suppressors on the DST who had normal urinary free cortisol concentrations responded to treatment, compared with only seven (44%) of the 16 patients characterized by nonsuppression of cortisol and/or elevated urinary free cortisol excretion. The relation between response to cognitive behavior therapy and HPA activity was not explained by clinical measures of symptom severity. CONCLUSIONS: Results are consistent with the hypothesis that patients with increased HPA function are less responsive to psychotherapy and, hence, might require somatic interventions. It is proposed that the negative impact of hypercortisolism on neurocognitive function mediates this relationship.

Adolescent↗
PubMed1995

Growth hormone secretion timing in depression: clinical outcome comparisons.

Growth hormone (GH) secretion in the 100 minutes preceding sleep onset (preSO), as well as in the first half of the night (1st HN), was examined for a group of 13 healthy women and 43 women with recurrent depression who participated in a 3-year maintenance therapy study. GH studies were obtained at several points during treatment and every 3 months during maintenance, during which patients were randomly assigned to active drug or drug-free maintenance treatment cells for 3 years, or until recurrence of depression. Depressed patients were divided into subgroups according to their maintenance treatment assignment (active drug or drug free) and treatment outcome (completing in remission or having a recurrence). Imipramine caused an increase in the GH ratio in all subgroups. Protocol completers had a significantly larger imipramine-induced increase in the GH ratio than did recurrers. The difference in time of GH secretion relative to sleep onset was found to correlate with treatment outcome and was independent of medication status during maintenance.

Adult↗
PubMed1992

Plasma cholinesterase isozymes and REM latency in schizophrenia.

The relation between electroencephalographic sleep parameters and plasma cholinesterase isozymes was examined in a group of 19 unmedicated schizophrenic patients. Rapid eye movement (REM) latency was found to be significantly inversely correlated with isozyme 3 (mainly acetylcholinesterase). The results are discussed in relation to cholinergic involvement in the regulation of REM sleep and in the pathophysiology of schizophrenia.

Adult↗
PubMed1992

The effect of SRIF on the EEG sleep of normal men.

The aim of this investigation was to evaluate EEG sleep, especially measures of delta-wave sleep, during and after the administration of somatostatin (SRIF). Eleven normal men, ages 22-37 yr, were administered saline or SRIF (0.1 microgram/kg/min IV) over 160 min at bedtime. SRIF delayed sleep-related growth hormone (GH) secretion without altering the amount of GH available during the entire night of sleep. No changes in delta-wave sleep occurred during either the first 100 min of sleep or the remainder of the night. Furthermore, all major EEG sleep variables were not significantly different between the saline and SRIF infusion night. It would not appear that the peripheral administration of this dose of SRIF or the subsequent delay of GH release has quantitative effects on EEG measures of all-night sleep.

Adult↗
PubMed1992

Rhythmic vs homeostatic influences on mood, activation, and performance in young and old men.

Nine healthy old (80+ years) men were compared with nine healthy young (20-30 years) men in a protocol that required 36 hours of continuous wakeful bedrest. Body temperature rhythm measurement confirmed that the old had as robust an endogenous circadian (approximately 24 hours) rhythm generation mechanism as the young. However, in measures of affect, activation, visual search speed, verbal reasoning speed, manual dexterity, and vigilance hit rate, the old showed a linear decline over the 36 hours of the vigil, with little of the superimposed 24-hour rhythmicity that was apparent in the young. Thus, separate from the endogenous rhythm generation processes, there appeared to be some attenuation with advanced age, which led to the relative absence of rhythmic expression in these mood and performance variables. Such attenuation might contribute to some of the sleep and performance problems reported by elderly adults.

Adult↗
PubMed1991

Acute effect of intravenous clomipramine upon sleep-related hormone secretion in depressed outpatients and healthy control subjects.

Tricyclic antidepressants have been used frequently as pharmacological probes in neuroendocrine studies even though they appear to lack neurochemical specificity. Despite this, the hormonal responses to these drugs have been used to provide evidence that depressed patients have alterations in both noradrenergic and serotonergic tone within the central nervous system. Most studies have been conducted in the morning, which is not a time of high physiological neuroendocrine secretory activity. The present study has used the relatively specific serotonergic probe intravenous clomipramine given to depressed patients and healthy subjects immediately before sleep onset, which is a time of increased neuroendocrine activity. Under these conditions, 12.5 mg clomipramine stimulates the secretion of both cortisol and prolactin, but unlike studies conducted in the morning, clomipramine suppresses the secretion of growth hormone in both groups. These data suggest that serotonergic mechanisms are involved in the regulation of the secretion of these three hormones at the time of sleep onset.

Adult↗
PubMed1991

Immediate effects of intravenous clomipramine on sleep and sleep-related secretion in depressed patients.

An i.v. challenge dose of clomipramine (12.5 mg) was given to eight outpatients with major depression. The procedure facilitated the examination of all-night sleep and sleep-related neuroendocrine changes (cortisol, growth hormone, and prolactin). In comparison to baseline saline nights, the patients experienced a profound suppression of rapid eye movement (REM) sleep throughout the night with no rebound recovery in the second half of the night. Furthermore, REM-suppressing effects were noted on the following no-drug night. In contrast, little effect on delta wave sleep was found, except for increased consolidation of delta waves within stage 3 and 4 sleep. Delta sleep measures were significantly correlated with levels of cortisol and growth hormone.

Adult↗
PubMed1991

Electroencephalographic sleep in the healthy "old old": a comparison with the "young old" in visually scored and automated measures.

This report extends the normative study of sleep into healthy 80-year-olds and compares them with healthy 70- and 60-year-olds. We observed stability of sleep efficiency and rapid eye movement sleep across three decades of late life, but a slight decline of slow-wave sleep in the 80-year-olds (decreased total delta wave counts). Women showed better preservation of slow-wave sleep than men. Automated EEG period analysis of this phenomenon demonstrated higher rates of delta wave production in the first NREM sleep period of women compared to that of men, a finding associated with longer REM sleep latencies in women. Unexpectedly, 80-year-old women showed decay in sleep maintenance, while 80-year-old men demonstrated stability of sleep maintenance, relative to their respective 60- and 70-year-old counterparts. Implications for the understanding of sleep and its regulation in health and aging are discussed.

Aged↗
PubMed1991

Circadian characteristics of healthy 80-year-olds and their relationship to objectively recorded sleep.

Thirty-four healthy older adults (self-described "good sleepers") in their ninth decade of life (16m/18f, mean age 83.1) were compared to 30 young controls in their third decade (21m/9f, mean age 25.5) with regard to: (a) circadian and personality characteristics as measured by the Horne-Ostberg Morningness Questionnaire (HOM), Circadian Type Questionnaire (CTQ) and Eysenck Personality Inventory (EPI); (b) measures of habitual bedtime, waketime, and time in bed from a 2-week sleep diary; and (c) polysomnographic measures from a (post-adaptation) night of sleep recording in the laboratory. In almost all laboratory measures the older group slept poorly compared with the young, acquiring about one hour less total recorded sleep. The older group showed earlier habitual time of waking than the young, and showed higher (more "morning-type") scores on test instruments (HOM, CTQ-M) designed to assess morning-evening orientation. They also showed a lack of flexibility in sleep patterns (higher CTQ-Rs score) and less intersubject and intrasubject variability in habitual sleep timing compared to the young. Older subjects' morningness test scores were significantly associated with objectively measured sleep durations, with a tendency toward "morning-type" circadian orientation being associated with longer sleep.

Adult↗
PubMed1991

The effect of GRF on the EEG sleep of normal males.

The administration of GRF in young men either before sleep onset or coinciding with sleep onset leads to an immediate significant increase in GH secretion. These increases were not associated with major alterations in sleep including slow-wave sleep.

Adult↗
PubMed1990

Minute-by-minute analysis of REM sleep timing in major depression.

Sleep changes described in depressed patients may represent alterations in the timing of rapid-eye-movement (REM) sleep or sleep onset. We examined these variables in groups of healthy control subjects (n = 47), depressed outpatients (n = 98), and depressed inpatients (n = 41). Outpatient depressives had greater severity of clinical symptoms than inpatients using the Hamilton Rating Scale for Depression. The depressed inpatient group had a later mean sleep onset time than the other groups, and the depressed outpatient group had a wider range of good night times than control subjects. REM timing in each group was examined as a relative frequency distribution of REM sleep (FDRS) for each minute across the night. The FDRSs for the three groups were statistically compared using the parameters from a two-component model, which includes a deterministic sinusoidal function and a time series process for errors. The slope of the linear trend in the FDRS rhythm was smaller (less positive) for both depressed groups than for controls. The ultradian FDRS rhythm occurred at an earlier phase, relative to sleep onset, in the inpatient depressed group compared to the control group. The ultradian FDRS rhythm had a longer period in the outpatient group compared to the control and inpatient groups. When referenced to 24-hr clock time in an exploratory analysis, the depressed groups appeared to have less robust FDRS ultradian rhythms than controls, but they did not appear to have a systematic phase alteration compared to controls. Abnormalities of REM sleep timing in groups of depressed patients may reflect a disturbance of sleep initiation and generation, or difficulty in entrainment of REM, rather than a systematic phase alteration in REM sleep propensity.

Adult↗
PubMed1990

Sleep, gender, and depression: an analysis of gender effects on the electroencephalographic sleep of 302 depressed outpatients.

Gender-related differences in electroencephalographic (EEG) sleep were examined in 151 pairs of men and women with major depression, all outpatients, matched for age and severity of depression. Across five decades (age 21-69), depressed men had less slow-wave sleep than did depressed women. Gender differences were small with respect to visually scored measures of slow-wave sleep time and percent, but moderate for gender differences in automated measures of slow-wave density. The time constant of the polygraph preamplifier significantly affected both visually scored and automatically scored slow-wave sleep. Other measures such as REM sleep latency, first REM period duration, sleep efficiency, and early morning awakening, showed robust age effects, but no main effects for gender or gender-by-age interactions. Gender effects on slow-wave sleep and delta-wave counts in depression parallel gender effects seen in healthy aging. The possibility of occult alcohol use by depressed male outpatients cannot be definitely excluded as a partial explanation of the current findings. However, covarying for past alcohol abuse did not negate the statistical significance of the observed gender effects on slow-wave sleep and delta-wave density. The possibility of gender differences in slow-wave regulatory mechanisms is suggested, but similarity in temporal distribution of delta-wave density between the first and second non-rapid-eye-movement (NREM) periods does not support gender differences in slow-wave sleep regulation.

Adult↗
PubMed1990

A reexamination of the relationship between growth hormone secretion and slow wave sleep using delta wave analysis.

Sleep onset growth hormone secretion is a reliable and reproducible finding in young adults and children. Secretion typically occurs during the first non-REM period of sleep and, despite some evidence to the contrary, growth hormone secretion has frequently been associated with the first period of slow wave sleep. By measuring delta wave activity (0.5-2 Hz) instead of slow wave sleep and, accounting for the within subject variability, it has not been possible to demonstrate a consistent or statistically significant linear relationship between delta wave activity and sleep-related growth hormone secretion. This suggests the presence of more complex mediating factors and the possibility that sleep onset and growth hormone secretion are two separate processes which are independently stimulated by events associated with sleep onset.

Adolescent↗
PubMed1990

Recurrent depression is associated with a persistent reduction in sleep-related growth hormone secretion.

Sleep onset is a powerful physiologic stimulus for growth hormone secretion. Difficulty falling asleep and poor sleep maintenance are prominent symptoms in patients with a major depressive disorder. Much of the disturbance in the sleep electroencephalograms of depressed patients occurs within the first half of the night, the time when growth hormone is usually secreted. Growth hormone secretion was measured during electroencephalographically monitored sleep in 38 patients with a recurrent major depressive disorder and 35 healthy control subjects. Before treatment, depressed patients had a statistically significant reduction in growth hormone secretion during sleep. This reduction, which persisted through treatment and recovery into the drug-free remitted state, may be a trait marker in patients with a recurrent depressive disorder.

Adult↗
PubMed1990

Three-year outcomes for maintenance therapies in recurrent depression.

We conducted a randomized 3-year maintenance trial in 128 patients with recurrent depression who had responded to combined short-term and continuation treatment with imipramine hydrochloride and interpersonal psychotherapy. A five-cell design was used to determine whether a maintenance form of interpersonal psychotherapy alone or in combination with medication could play a significant role in the prevention of recurrence. A second question was whether maintaining antidepressant medication at the dosage used to treat the acute episode rather than decreasing to a "maintenance" dosage would provide prophylaxis superior to that observed in earlier trials in which a maintenance dosage strategy was employed. Survival analysis demonstrated a highly significant prophylactic effect for active imipramine hydrochloride maintained at an average dose of 200 mg and a modest prophylactic effect for monthly interpersonal psychotherapy. We conclude that active imipramine hydrochloride maintained at an average dose of 200 mg is an effective means of preventing recurrence and that monthly interpersonal psychotherapy serves to lengthen the time between episodes in patients not receiving active medication.

Adult↗