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Biomedical subjects

S C Risch

Publications and source records attributed to S C Risch.

At least 19 recordsLinked to original sources
PubMed1992

Controlled trial of bright light for nonseasonal major depressive disorders.

Psychotropic drug-free hospitalized veterans with nonseasonal major depressive disorders or depressed forms of bipolar disorder were treated with light for 1 week. Twenty-five patients were randomly assigned to bright white light treatment (2000-3000 lux), and 26 patients were randomized to dim red light placebo control treatment. Unlike those treated with dim red light, those treated with bright white light showed declines in three measures of depression during treatment. Partial relapse appeared within 2 days. A global depression score showed a statistically significant (p = 0.02) difference favoring bright white light treatment. Two bright-light-treated patients became mildly hypomanic, but side effects were mild. Improvement was not correlated with patient expectations; indeed, patients expected somewhat greater benefit from the placebo. Patients treated in summer responded as well as those treated in winter. Baseline electroencephalogram (EEG) sleep stage data (e.g., rapid eye movement; REM latency) did not predict treatment responses. These 1-week treatment results suggest that bright light might produce benefits for patients with nonseasonal depression. Bright light should not be recommended for routine clinical application before additional assessments with longer treatment durations are done.

Adult↗
PubMed1992

Plasma beta-endorphin and natural killer cell activity in major depression: a preliminary study.

Low concentrations of beta-endorphin have been found to enhance human natural killer (NK) cell activity in vitro. Both beta-endorphin and NK activity are changed by clinical depression. To evaluate whether circulating concentrations of beta-endorphin have a role in the in vivo modulation of cellular immunity in humans, we measured plasma beta-endorphin and NK cell activity in 14 depressed patients and 14 age-matched control subjects. In the depressed patients, both plasma beta-endorphin and NK cell activity were reduced to 76% and 57%, respectively, of the mean levels in the control subjects. In addition, beta-endorphin showed a significant positive correlation with lytic units of NK cell activity in the combined group of all subjects and in the patient group (p = 0.04), but not in the control group. The study supports the hypothesis that circulating endorphin is correlated with NK cell activity in vivo. This correlation may be higher in the depressed patient group.

Adult↗
PubMed1992

White matter hyperintensity signals in psychiatric and nonpsychiatric subjects.

OBJECTIVE: As part of an ongoing study investigating the relationship between brain morphology/function and neuropsychological performance in psychopathology, the authors conducted brain magnetic resonance imaging (MRI) studies to investigate the prevalence and psychiatric significance of white matter hyperintensity signals. METHOD: Brain MRI acquisition was done with 0.5 and 1.5 Tesla Philips scanners. Psychiatric subjects (N = 229) and normal volunteers (N = 154) were recruited by newspaper and local advertising and by physician referral. DSM-III-R criteria were used. White matter hyperintensity signals were rated on a 4-point scale of severity. Prevalence rates and risk ratios were calculated. RESULTS: Prevalence rates of hyperintensity signals in all psychiatric subjects (mean age = 34 years, SD = 9) and normal volunteers (mean age = 34, SD = 10) were 6.6% and 9.1%, respectively (a nonsignificant difference). When all psychiatric subjects, subjects under age 45, and subjects age 45 and over in a diagnostic category were considered, there were no statistically significant differences between them and normal volunteers in the same age groups in prevalence of schizophrenia, schizoaffective disorder, bipolar disorder, major depression, and obsessive-compulsive disorder. A significant difference existed between the severity of deep white matter hyperintensity signals in subjects with major depression and normal volunteers. Older age was correlated as a risk factor for white matter hyperintensity signals for psychiatric subjects. CONCLUSIONS: These results do not support previous findings of greater prevalence of hyperintensity signals in bipolar disorder. Significantly higher prevalence rates of hyperintensity signals were seen in subjects with major depression only when severity of the deep white matter hyperintensity signals was considered. Older age is an indirect risk factor for the presence of white matter hypertensity signals, probably as a result of vascular changes associated with concurrent medical illnesses.

Adult↗
PubMed1992

Association of beta-endorphin with specific clinical symptoms of depression.

OBJECTIVE: Abnormalities in plasma concentrations of beta-endorphin-like immunoreactivity (beta-endorphin) have been reported in depressed patients. This study was done to test the hypothesis that specific clinical characteristics of depression are associated with plasma beta-endorphin concentration. METHOD: Plasma beta-endorphin was evaluated in 20 depressed patients diagnosed according to DSM-III-R and in 23 age- and sex-matched comparison subjects, and each was evaluated with the structured Schedule for Affective Disorders and Schizophrenia (SADS). Twelve SADS items involving dysphoric mood and related symptoms were chosen for analysis. RESULTS: Within the group of all 43 subjects and within the depressed group, beta-endorphin level correlated significantly with psychic anxiety and with phobia. In the depressed group only, beta-endorphin also correlated significantly with obsessions/compulsions. Concentration of beta-endorphin was not significantly correlated with score on the Hamilton Rating Scale for Depression or Beck Depression Inventory or with scores on other SADS symptom items, including somatic anxiety, insomnia, subjective anger, overt anger, agitation, psychomotor retardation, panic attacks, appetite loss, or total weight loss. In the group of 23 comparison subjects, beta-endorphin did not correlate with Beck or Hamilton depression score or with any of the SADS clinical variables. CONCLUSIONS: High levels of plasma beta-endorphin may be associated with more severe anxiety, phobia, and obsessions/compulsions in depressed patients.

Adult↗
PubMed1992

CSF 5-HIAA as a predictor of treatment response in trichotillomania.

Trichotillomania is characterized by chronic hair-pulling resulting in noticeable hair loss. In a preliminary study, cerebrospinal fluid (CSF) measures in 8 medication-free, female, trichotillomania patients were compared to those of matched, normal controls. There was no difference between patients and controls in measures of CSF cortisol, 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG). CSF measures did not correlate with measures of trichotillomania symptomatology. However, degree of response to treatment with serotonin re-uptake inhibitors significantly correlated with baseline CSF 5-HIAA. This suggests that central serotonin turnover is specifically relevant to treatment response to serotonin re-uptake inhibitors in trichotillomania.

Adult↗
PubMed1992

Limbic-hypothalamic-pituitary-adrenal axis activity and ventricular-to-brain ratio studies in affective illness and schizophrenia.

Some investigators have speculated that structural brain alterations observed in some psychiatric patients might be related to increased limbic-hypothalamic-pituitary-adrenal axis (LHPA) activity. To explore this hypothesis, we prospectively studied 166 research volunteers (19 patients with research diagnostic criteria (RDC) major depression, 9 patients with RDC bipolar depression, 45 patients with RDC schizophrenia, and 94 RDC normal controls), examining the relationship between magnetic resonance image-determined ventricular-to-brain ratio (VBR) and indices of LHPA axis function (cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF), CSF adrenocorticotropic hormone (ACTH), and 24-hour urinary-free cortisol secretion). We observed no significant differences in mean VBR among the three patient groups and the normal control volunteers. Of the indices of LHPA activity, only CSF CRF concentrations distinguished the four subject groups, with CSF CRF being significantly elevated in the more severely depressed major depression patients. Indices of LHPA activity were not significantly correlated with VBR in any of the three patient groups or in the normal volunteers. These preliminary results suggest that VBR is not highly associated with alterations in LHPA activity, at least as determined cross-sectionally. Further longitudinal studies with reference to diagnostic subtypes, severity, symptom profiles, and more specific neuroanatomic regions may allow the elucidation of possible relationships between LHPA pathology and structural brain alterations.

Adrenocorticotropic Hormone↗
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↗