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Biomedical subjects

S C Risch

Publications and source records attributed to S C Risch.

At least 37 records · Page 2Linked to original sources

Differences in qualitative brain morphology findings in schizophrenia, major depression, bipolar disorder, and normal volunteers.

This study examined the frequency and type of qualitative brain morphologic anomaly as a function of sex and diagnosis. Magnetic resonance imaging brain scans were evaluated by an experienced neuroradiologist blind to diagnosis. The scans of 325 individuals (108 schizophrenic, 20 schizoaffective, 27 major depressive, 20 bipolar and 150 healthy volunteers) were categorized into one of five groups: normal, hyperintensity signals, volume loss, ventricular anomaly or "other" abnormality. Schizophrenic men had significantly more morphologic anomalies, especially of the lateral ventricles than healthy male volunteers. Schizophrenic women did not differ from healthy women. Schizoaffective patients of both sexes, male depressive and female bipolar patients were also characterized by higher rates of brain anomalies. Independent of diagnosis, women were more likely than men to have hyperintensity signals among individuals with positive scan findings. The overall rate of brain morphologic anomalies is significantly higher among male schizophrenic patients than healthy volunteers; this is not specific to male schizophrenics, however, suggesting a global sex effect. Type of anomaly may differ by sex and give us clues about sex differences in the pathophysiology of psychopathology.

Adult↗

Clozapine-induced EEG abnormalities and clinical response to clozapine.

The authors hypothesized that patients who develop gross EEG abnormalities during clozapine treatment would have a less favorable outcome than patients who did not develop abnormal EEGs. The clinical EEGs and the Brief Psychiatric Rating Scale (BPRS) scores of 12 patients with schizophrenia and 4 patients with schizoaffective disorder were compared before and during treatment with clozapine. Eight patients developed significant EEG abnormalities on clozapine; 1 showed worsening of an abnormal pre-clozapine EEG; none of these subjects had clinical seizures. BPRS scores improved significantly in the group of patients who developed abnormal EEGs but not in the group who did not. Findings are consistent with previous reports of a high incidence of clozapine-induced EEG abnormalities and a positive association between these abnormalities and clinical improvement.

Adult↗

Illness characteristics of patients in clinical drug studies of mania.

Two recent large-scale studies of the effectiveness and safety of divalproex versus lithium and placebo in the manic phase of bipolar disorder have provided an opportunity to investigate the characteristics of patients enrolled in clinical drug trials of mood stabilizers. Both studies are randomized, double-blind, parallel-group, multicenter trials; the first addresses effectiveness in acute mania, and the second addresses effectiveness in prevention of manic episodes. Data on demographic, illness severity, and treatment response characteristics were compared between Study 1 and six other clinical drug trials in acute mania from the past decade that had data in comparable domains. Although patients experienced onset of bipolar disorder in their early twenties, the average age of enrollment in the studies was about 40. Approximately equal numbers of men and women were enrolled. The patients were severely ill at the time of enrollment, with mean scores on the Global Assessment Scale ranging from 20 to 37. Overall, characteristics were remarkably similar across studies and representative of those reported in epidemiological studies. From Study 2, which is currently in progress, characteristics of patients recruited into the trial were determined. At least 10 subjects were initially assessed for each subject actually enrolled in the trial. The two factors most associated with failure to move from the open phase of the study to the randomized phase were administrative problems (principally failure of subjects to adhere to the medication regimen and protocol requirements) and inability, even with an open treatment protocol, to achieve adequate recovery from the index manic episode within 3 months.

Adolescent↗

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↗

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↗

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↗

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↗

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↗

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↗