Biomedical subjects
Publications and source records attributed to A Winokur.
Cosyntropin (ACTH alpha 1-24) infusion caused significantly higher cortisol concentrations, with earlier peak responses, in patients with endogenous depression than in normal subjects. There was no relationship between the cortisol levels after administration of dexamethasone and cosyntropin.
The effect of deafferentation of the rat olfactory bulb on bulbar TRH concentration was studied. TRH concentrations in the lesioned bulbs did not decline when compared to concentrations in sham-lesioned bulbs for the post-lesion intervals of 1 h through 14 days. Since TRH concentrations did not decline following deafferentation, TRH in the olfactory bulb does not derive from centrifugal neurons.
We have measured the endogenous TRH concentration in the pineal and 9 brain regions of a seasonal hibernator, the golden-mantled ground squirrel, during euthermia and hibernation in order to investigate the possibility that changes in TRH concentration might occur in association with naturally-occurring changes in CNS-mediated physiological and behavioral processes. Regional TRH content was assessed by radioimmunoassay in adult animals that were killed during euthermia in the mid-portion of each season and during hibernation in mid-winter. No significant changes in TRH concentration related to season or to hibernation versus euthermic state were noted in the hippocampus, brainstem, or cerebellum. In the olfactory bulb, preoptic area, and pineal, seasonal variation within euthermic groups was evident. During hibernation, statistically significant decreases in TRH content occurred in the forebrain, olfactory bulb, hypothalamus, septum, preoptic area, and midbrain. Significant fluctuations during hibernation were also observed in the pineal. In this structure, TRH concentration varied in relation to the phase of the hibernation bout. TRH content in the last quarter of the bout was three times greater when compared to values observed in the first quarter of the bout. These results suggest that TRH may be involved in the control processes attributed to these regions and support a role for TRH in the neural control of hibernation.
Growth hormone (GH), prolactin (PRL) and thyrotropin (TSH) release following gonadotropin-releasing hormone (GnRH) administration were examined in 56 patients with major affective disorder (37 unipolar, 19 bipolar) and 38 normal healthy subjects. There were no differences in GH, PRL or TSH responses after GnRH infusion between the patients and the normal subjects, in contrast to previously reported abnormalities in depressed patients. Serum GH concentration increased after GnRH in both normal and depressed men; serum TSH increased after GnRH in both normal women and bipolar women, but not in unipolar depressed women. Further studies comparing GnRH to saline infusion will be necessary to determine if the GH and TSH responses seen in this study are due to GnRH or result from the stress of the experimental procedures.
Administration of thyrotropin releasing hormone (TRH), 400 micrograms i.v., to healthy premenopausal women resulted in improvement in ratings of tension on the 100 mm line test. The max. mean improvement in tension ratings was significantly greater after TRH than after saline (t = 2.27, df = 9, p less than 0.05); after TRH administration, eight of 10 subjects showed greater than 30% improvement in tension ratings, while only three of 10 subjects receiving saline reported a comparable degree of improvement. No significant improvement in ratings of mood state were noted after administration of either TRH or saline. These findings extend previous reports of behavioral effects of TRH in normal subjects. The possibility that the behavioral effects of TRH may be influenced by the state of activity of the CNS is discussed.
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Abnormalities of hormonal responses to a number of neuroendocrine challenges have been reported in depressed patients. The authors used a series of four neuroendocrine challenges-thyrotropin-releasing hormone (TRH) and gonadotropin-releasing hormone (GnRH) stimulation, insulin tolerance test (ITT), and overnight dexamethasone suppression test (DST)-and examined eight hormonal responses in 24 healthy subjects and 26 patients with primary unipolar affective disorder. Seven control subjects (29.2%) and 25 depressed patients (96.2%) had at least one abnormal response, and 15 depressed patients (57.7%) had two or mor abnormal responses. These findings suggest that depressed patients show variability in hormonal response across a number of neuroendocrine axes. No consistent patterns of abnormality of hormonal response were observed.
The authors report data on the overnight dexamethasone suppression test (DST) from 64 patients with primary affective disorder (41 unipolar, 17 bipolar-depressed, and 6 bipolar-hypomanic) and 53 healthy control subjects. No difference between the patients and controls was noted in baseline 8:00 a.m. serum cortisol levels or in cortisol levels obtained after the administration of 1 mg of dexamethasone. Sixteen patients and 8 controls had 4:00 p.m. postdexamethasone cortisol levels higher than 5.0 micrograms/dl. The distribution of suppressors and nonsuppressors did not differ significantly between the two groups. Patient nonsuppressors had significantly higher baseline cortisol levels than did patient suppressors (p less than .001). Clinical parameters and family history data did not distinguish patient suppressors from nonsuppressors.
Amitriptyline-perphenazine (100/8-150/12 mg/day) and doxepin (100-150 mg/day) were compared for clinical efficacy and safety in a sample of 130 nonpsychotic depressed outpatients. Maximum study duration was 4 weeks; 19 amitriptyline-perphenazine and 29 doxepin patients completed less than or equal to 3 weeks of treatment and 45 amitriptyline-perphenazine and 37 doxepin patients completed 4 weeks of treatment. Patients in both groups showed significant improvement in depression, but amitriptyline-perphenazine produced greater improvement than doxepin on several measures of depressive symptomatology. The incidence of anticholinergic and sedative side effects was higher in the amitriptyline-perphenazine treated group.
Thyrotropin-releasing hormone was microinjected into the dorsal hippocampus of ground squirrels (Citellus lateralis) when they were at different levels of arousal, as assessed by electrophysiological and behavioral criteria. When administered to the awake animal, thyrotropin-releasing hormone produced dose-dependent decreases in body temperature accompanied by behavioral quieting and reductions in metabolic rate and electromyographic activity. The magnitude of these effects was greater when the peptide was microinjected during a period of behavioral activation. In contrast, administration of the peptide during slow wave sleep produced increased thermogenesis, an increase in electromyographic activity, and an increase in the amount of electroencephalographic desynchronization.
We report that the rat olfactory bulb is rich in thyrotropin releasing hormone (TRH) immunoreactivity. TRH content was determined according to the radioimmunoassay method of Bassiri and Utiger. The concentration (mean +/- SEM., n = 10) of TRH in olfactory bulb (60 +/- 10 pg/mg wet weight) was 23% of the concentration in the hypothalamus, and was at least twice that of other brain regions examined. The 2 olfactory bulbs (mean wet weight 65 mg/2 bulbs) contained 3.9 +/- 0.3 ng TRH. The TRH immunoreactivity could be separated into high and low molecular weight forms. The low molecular weight form co-chromatographed with authentic TRH (mol. wt. 362) on gel filtration and thin layer adsorption chromatography and caused the release of thyrotropin from pituitary tissue incubated in vitro. Since the neuronal organization and functions of the olfactory bulb are well described, studies of the localization and metabolism of TRH in this region may help to clarify the role of this tripeptide in the central nervous system.
Considerable attention has been paid to studies of hormonal response abnormalities in depressed patients, and functional changes have been demonstrated in a number of neuroendocrine axes. The findings from the present study extend the results of previous investigations but demonstrate a functionally intact HPG axis in depressed patients. A number of statements can be made concerning the gonadotropin-releasing hormone (GnRH) strategy: (1) Previous studies utilizing GnRH challenge have been limited in number and poorly controlled. (2) We chose to utilize our normative data because standard gonadotropin response ranges to GnRH have not previously been established in studies with depressed patients. Moreover, hormonal responses may be affected by age, sex, menstrual status, dose, and method and rate of GnRH administration. The assessment of the hormonal responses to GnRH in depressed patients and healthy controls studied under identical conditions provides the most accurate basis for comparison. (3) The incidence of abnormal LH and FSH release in depressed subjects was similar to controls, in contrast to response abnormalities found with other neuroendocrine axes. (4) Alterations in gonadotropin were limited to FSH, were sporadic, and did not differ significantly from controls. This finding is of interest and suggests that neuroendocrine alterations in depression do not necessarily affect all neuroendocrine axes.
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There is evidence for functional changes in the hypothalamic-pituitary-gonadal axis of patients with affective disorders. Little is known concerning spermatogenesis or sperm function in depressed men. We systematically evaluated the sperm indices in a group of depressed males complaining of diminished libido, and a healthy control group. No differences were noted in sperm parameters between the groups.
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Twelve depressed outpatients were studied to determine if tricyclic antidepressants affect the dexamethasone suppression test (DST). The authors administered the DST to patients while they were drug free and 3 weeks after they had taken tricyclics. The difference between tests was not significant.
Imipramine has been shown to have a potent inhibitory effect on sperm motility in vitro. Because of the frequent chronic use of antidepressants in treatment of depression, we investigated the in vivo effects of desmethylimipramine and lithium carbonate on sperm function in patients suffering from clinical depression. We also studied the in vitro effects of a series of neurotrophic agents on sperm motility. There were no significant differences in sperm count, viability, or motility between a group of patients diagnosed as having clinical depression and a group of semen donors with normal sperm characteristics. Three weeks of continuous therapy with desmethylimipramine or lithium carbonate resulted in a significant decrease in sperm viability but no significant change in sperm count or motility. The in vitro drug studies demonstrated that imipramine hydrochloride, desmethylimipramine, chlorpromazine, trifluoperazine, and nortriptyline hydrochloride were all potent inhibitors of sperm motility, whereas lithium carbonate had no effect on motility.