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Biomedical subjects

S C Risch

Publications and source records attributed to S C Risch.

At least 55 records · Page 3Linked to original sources
PubMed1992

Neurochemical alterations of serotonergic neuronal systems in depression.

A burgeoning literature has accumulated over the past three decades implicating alterations in central nervous system (CNS) serotonergic neurotransmission both in the pathophysiology of depression and in the mechanism and action of antidepressant drug treatment. Specifically, studies have revealed (1) decreases in brain concentrations of serotonin and decreases in cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in a sizeable subgroup of depressed patients; (2) alterations in both presynaptic and postsynaptic CNS serotonergic receptors in depressed patients; (3) alterations in putative peripheral markers of CNS serotonergic function such as platelet serotonin uptake, platelet [3H]imipramine or [3H]paroxetine binding, platelet 5-HT2 receptor density, and whole blood serotonin content in depressed patients; (4) that virtually all known antidepressant agents, regardless of their receptor-specific properties, have been shown to increase the efficacy of CNS serotonergic neurotransmission; (5) that in patients treated with antidepressants who exhibit a remission, rapid depletion of serotonin results in a prompt clinical relapse; and (6) that all known serotonin re-uptake blockers thus far studied have been demonstrated to be clinically effective antidepressant medications. The recent identification and cloning of multiple serotonergic receptor subtypes and the identification and cloning of the serotonin transporter offer further promise for elucidating the role of CNS serotonergic neurons in the pathogenesis of depression and, moreover, for the development of innovative treatment strategies for this disorder.

Antidepressive Agents↗
PubMed1991

The effects of scopolamine on sleep and mood in depressed patients with a history of alcoholism and a normal comparison group.

In order to determine the effect of an anticholinergic agent on mood and sleep, scopolamine (0.4 mg IM) was administered before bedtime for three consecutive nights to 10 depressed patients (8 with a history of alcohol abuse) and 10 normal comparison subjects. The patients had a small, statistically significant antidepressant response on the second morning of treatment. Scopolamine inhibited rapid eye movement (REM) sleep and prolonged REM latency equally in depressed patients and the normal comparison group. Partial tolerance to the REM inhibiting effect of scopolamine developed between the first and third night of treatment. A REM rebound occurred during recovery nights. These results are consistent with concepts relating central cholinergic mechanisms to the control of REM sleep. Compared with controls, patients showed a greater increase in Stage 2 and Stage 2% and a lesser and increase in Delta (Stage 3 and 4) sleep % and Stage 4% on the first night of treatment. Further, well-controlled studies are needed to determine whether anticholinergic drugs possess clinically significant antidepressant effects.

Adult↗
PubMed1991

The effects of physostigmine infusion on patients with panic disorder.

Nine patients who met both DSM-III and RDC criteria for panic disorder and nine age-matched normal controls received infusions of physostigmine. The patients and normal controls did not differ in either their self-reported or the observer-reported ratings of anxiety, mood, or activation. The two subject groups also did not differ in blood pressure, pulse, or cortisol responses to physostigmine. Physostigmine did not provoke panic attacks in either the control or patients groups.

Adult↗
PubMed1991

The cholinergic rapid eye movement induction test with arecoline in depression.

The cholinergic rapid eye movement (REM) induction test using arecoline hydrobromide, a cholinergic muscarinic receptor agonist, was studied in patients with affective disorder and in normal controls to determine whether or not depression is associated with enhanced induction of REM sleep by muscarinic agonists. Arecoline induced REM sleep in a dose-dependent fashion in both patients and controls compared with placebo infusions. Compared with normal controls, patients entered REM sleep significantly more rapidly following intravenous administration of 1.0 mg of arecoline hydrobromide than they did following administration of 0.5 mg of arecoline hydrobromide or placebo. These results, as well as those of previous studies, support the hypothesis that patients with affective disorder show a functional supersensitive induction of REM sleep in response to muscarinic receptor agonists and may be consistent with the hypothesis that functional muscarinic receptor "up regulation" is associated with depression.

Arecoline↗
PubMed1991

Lateral ventricle-brain ratio and balance between CSF HVA and 5-HIAA in schizophrenia.

OBJECTIVE: Lateral ventricle enlargement in schizophrenia has been positively correlated with poor premorbid competence, negative symptoms, and poor treatment response and negatively correlated with concentrations of homovanillic acid (HVA), a dopaminergic metabolite. The authors provide further evidence of a reciprocal relationship between lateral ventricle size and dopaminergic activity in schizophrenia. METHOD: They assessed the relationship between lateral ventricle enlargement (ventricle-brain ratio, VBR) and CSF neurotransmitter metabolite concentrations (HVA and 5-hydroxyindoleacetic acid [5-HIAA]) in 45 patients with schizophrenia, 28 with affective disorders (19 patients with major depression and nine with bipolar disorder), and 91 normal comparison subjects. RESULTS: No group mean differences were significant. Although individual correlations of VBR with HVA and 5-HIAA were not statistically significant, the ratio of HVA to 5-HIAA was significantly correlated with VBR in the patients with schizophrenia, a finding consistent with dopaminergic-serotonergic balance hypotheses. CONCLUSIONS: These data suggest that it is the balance between HVA and 5-HIAA rather than their absolute levels which is associated with brain morphology and that this relationship between brain chemistry and morphology may be characteristic of the normal range of functioning for these systems. In other words, independent of whether brain morphology and chemistry differentiate psychopathological from nonpsychopathological states, there may be an orderly relationship between lateral ventricle size and the balance between HVA and 5-HIAA balance that is especially prominent in schizophrenia.

Adult↗
PubMed1990

Sexual dimorphism, brain morphology, and schizophrenia.

The study of sexual dimorphism in brain morphology may help delineate subtypes of schizophrenia based, in part, on sex; yield insight into the relationship between brain structure and behavior; and provide a neurodevelopmental context for studying the ontogenesis of schizophrenia. Preliminary findings from an ongoing study of sex differences in brain morphology and neuropsychological performance in schizophrenia suggest that schizophrenic males are characterized by multiple morphological deviations; this may represent an extreme form of normal sexual dimorphism in brain morphology. The role of brain morphology deviation in the ontogenesis of schizophrenia is discussed.

Adult↗
PubMed1989

Augmented pituitary corticotropin response to a threshold dosage of human corticotropin-releasing hormone in depressives pretreated with metyrapone.

We studied pituitary corticotropin response to exogenous corticotropin-releasing hormone infusion and attempted to control for the confounding effect of variable serum cortisol levels between depressed and control subjects. If metyrapone was given during the time of day when hypothalamic pituitary adrenal activity was otherwise low, the relative increase in the corticotropin concentration was small. Pituitary response to exogenous corticotropin-releasing hormone can be defined under conditions in which the amount of glucocorticoid-mediated negative feedback present at the level of the pituitary gland is equal in all subjects. When the ambient cortisol level was equalized (and suppressed) in all subjects at the time of study with a threshold dosage of corticotropin-releasing hormone, we found an augmented response to corticotropin-releasing hormone in depressives. This raises the possibility that either increased pituitary sensitivity to corticotropin-releasing hormone or an increased intracellular pool of corticotropin is available for release in subjects with major depressive illness.

Adrenocorticotropic Hormone↗
PubMed1989

Mitogen-stimulated lymphocyte proliferation and pituitary hormones in major depression.

To assess cellular immune status and the hypothalamic-pituitary (HP) axis in patients with major depression, we examined peripheral blood mononuclear cells (PBMC) and measured the plasma levels of cortisol, adrenocorticotropin hormone (ACTH), growth hormone (GH), and prolactin (PRL). Twenty patients with major depression were compared with 20 control subjects matched for age, sex, and race. The dose-response curves for concanavalin-A (Con-A) and phytohemagglutinin (PHA) stimulation were not significantly different between the two groups. The patients had decreased Con-A-stimulated T-lymphocyte proliferation when compared to the control subjects, but only at the lowest suboptimal concentration of Con-A. None of the four concentrations of PHA-stimulated proliferation were different between the two groups, neither was PHA-induced interleukin-2 production. Within the patient group only, plasma prolactin (PRL) correlated significantly with stimulated lymphocyte proliferation using two optimal concentrations of PHA and one optimal concentration of Con-A, when the proliferation was expressed using the stimulation index.

Adrenocorticotropic Hormone↗
PubMed1989

Neuroendocrine effects of ovine corticotropin-releasing hormone in panic disorder patients.

A number of neuroendocrine abnormalities have been reported in panic disorder patients: the most extensively studied being disturbances of hypothalamic-pituitary-adrenal function (Curtis et al. 1982; Leiberman et al. 1983; Uhde et al. 1988). The recent sequencing and synthesis of corticotropin-releasing hormone now allows direct testing of pituitary responsivity to this neuropeptide in affective and panic disorder patients (Holsboer et al. 1984; Gold et al. 1986; Roy-Byrne et al. 1986; Holsboer et al. 1987; Risch et al. 1988). We report the effects of intravenously administered ovine corticotropin-releasing hormone (0.03 micrograms/kg) on plasma concentrations of adrenocorticotropin hormone (ACTH) and cortisol in a small group of panic disorder patients and age- and sex-matched normal controls.

Adrenocorticotropic Hormone↗
PubMed1989

Lithium delays circadian phase of temperature and REM sleep in a bipolar depressive: a case report.

The effects of lithium on the circadian rhythms of body temperature and rapid eye movement (REM) sleep were examined in a patient with bipolar depression. The acrophase of body temperature showed a phase delay of 74 min after 1 week of lithium treatment. REM latency increased significantly with lithium, and the onset of subsequent REM periods was also delayed. The proportion of the night spent in REM sleep decreased significantly. There was no effect of lithium on the patient's mood. The data are consistent with the hypothesized phase-delaying properties of lithium but do not support the causal link between circadian phase and affective state.

Bipolar Disorder↗
PubMed1989

Effects of brief naps on mood and sleep in sleep-deprived depressed patients.

To determine the effects of brief naps on mood and electroencephalographic (EEG) sleep in sleep-deprived depressed patients, data from 19 hospitalized patients with depression were analyzed; all were kept awake from 0700h until the following day, when they were allowed 10-min naps at either 0830h or 1500h. Six of the patients showed a clinically significant improvement (greater than 40% change) on the Hamilton Rating Scale for Depression (HRSD) before the nap after all-night sleep deprivation, and the group as a whole showed a significant improvement on the HRSD, the Profile of Mood States, and the Brief Psychiatric Rating Scale subscale for depression. Naps did not alter mood in the responders, but did improve measured depression on the HRSD in the non-responders. Morning and afternoon naps did not differ significantly in their effects on mood or nap sleep. On the recovery sleep, patients who were classified as responders after the nap showed a significantly greater increase in delta (Stage 3 + 4) sleep compared with baseline than nonresponders.

Affect↗
PubMed1989

Biological effect of bright light.

1. Five minute bright light exposures reduced plasma levels of melatonin in eight normal subjects. 2. No significant change in ACTH levels occurred. 3. These results raise the possibility that short intense light exposures can synchronize circadian rhythms as well as benefit patients with seasonal affective disorder. They also indicate that short pulses of bright light do not affect pituitary ACTH production.

Adrenocorticotropic Hormone↗
PubMed1989

Blunted growth hormone response to peripheral infusion of human growth hormone-releasing factor in patients with panic disorder.

Patients with panic disorder (N = 11) and age- and sex-matched normal control subjects (N = 11) were challenged with human growth hormone-releasing factor (GH-RF) (1 microgram/kg i.v.) or placebo in random order. The control subjects had significantly increased plasma growth hormone (GH) levels after GH-RF infusion whereas panic disorder patients did not. At 15 and 30 minutes after GH-RF infusion, GH concentrations were significantly higher in the control subjects than in the patients. These findings with GH-RF extend findings from earlier reports that patients with panic disorder show blunted GH response to phobic stimulation and clonidine.

Adult↗
PubMed1989

Behavioral hyporeactivity to physostigmine in detoxified primary alcoholics.

Changes in anergia/inhibition, mood, and pulse rate induced by intravenous physostigmine were significantly less pronounced in 26 patients with primary alcoholism than in 36 normal control subjects. These results suggest possible abnormalities in central cholinergic functioning in primary alcoholics.

Adolescent↗
PubMed1988

Platelet serotonin transport after a single ECT.

Platelet 5-HT uptake was examined in six depressed patients before and after a single electroconvulsive treatment and compared with six age- and sex-matched controls. The depressed patients had a significantly (P less than 0.05) lower Vmax of platelet 5-HT uptake prior to ECT (22.9 +/- 7.6 pm/2 x 10 platelets) than did control subjects (37.5 +/- 9.1 SEM). After a single ECT treatment, the Vmax significantly (P less than 0.05) increased to levels (34.6 +/- 10.1)no longer significantly different from control. The results are compared with recent data from depressed patients indicating that low baseline levels of platelet imipramine binding increase after ECT treatment.

Adult↗