Biomedical subjects
Publications and source records attributed to R R Fieve.
A new self-rating scale, the General Behavior Inventory (GBI), was lower in eight controls and 61 patients in remission than in 32 depressed patients. Scores of depressed patients decreased over treatment time. GBI score correlated significantly with the past occurrence of manic plus depressive symptoms per visit and past mean mood shift per visit.
Platelet [3H]imipramine binding (Bmax) was determined in 67 patients with major affective illness (33 euthymic bipolar, 34 depressed unipolar) and 58 normal control subjects. Bipolar patients had significantly lower Bmax values than did control subjects. The mean Bmax in the unipolar patients was lower than in the control subjects, but the difference was not statistically significant. Dissociation constant (Kd) values did not distinguish patients in either category from control subjects. The significantly lower Bmax in euthymic bipolar patients and the apparent state independence of Bmax in some but not all unipolar patients suggest that platelet imipramine binding may be a trait marker in a subset of affective disorders.
Seventy patients with unipolar major depressive disorder were treated with fluoxetine or placebo in a 6-week double-blind trial and were evaluated by changes in scores on the Hamilton Rating Scale for Depression (HAM-D) and the global improvement measure of the Clinical Global Impressions (CGI) scale. High correlations were found between the changes in HAM-D scores from baseline to endpoint and the final CGI improvement ratings. In patients with moderate depression (baseline HAM-D score of 20 or more), the differences in endpoint analysis between active treatment and placebo groups were significant. A persistent pattern of improvement was noted in 27% of those receiving fluoxetine but in none of those receiving placebo. Physician and patient evaluations as determined by the improvement measure of the CGI were closely correlated.
75 outpatients who presented to an affective disorder clinic received the dexamethasone suppression test (DST). Following 1 week observation, and following 1 week on low-dose imipramine HCl, all patients who remained depressed (Hamilton score 16 or greater) were given a full clinical trial of imipramine HCl (150-300 mg/day) over a minimum 3- to 5-week period. Of the 45 patients who required this trial and who received imipramine HCl for at least 3 weeks, there was no relationship between DST suppression or nonsuppression vs. clinical response to imipramine HCl. There was a statistically significant trend for suppressors (negative DST) to respond either spontaneously or to low-dose imipramine HCl as opposed to nonsuppressors (positive DST).
There were no differences in interepisode functioning or side effects between bipolar patients (N = 44) with plasma lithium levels above the median and those with levels below the median. Low levels were able to stabilize mood and individual symptoms for 40.5 months.
A long-term epidemiological genetic study was conducted in which all new patients were evaluated prospectively at the Foundation for Depression and Manic Depression and two Lithium/Affective Disorders clinics at the Columbia-Presbyterian Medical Center between the years of 1972 and 1978. All patients met Feighner, RDC and DSM III criteria for Major Depressive Disorder after initial clinical screening interviews and were further subtyped using the Fieve-Dunner 7-point criteria. All 604 probands and 90% of 2711 first-degree relatives were interviewed blindly by diagnosticians trained in the use of the SADS structured interview. Cumulative morbid risk in parents, siblings and children of 490 bipolar probands was 15.6 +/- 3% and 14.0 +/- 1.7% in the first-degree relatives of 114 unipolar probands. A number of biological and genetic marker studies were simultaneously performed on samples of the overall population. The enzymes catechol O-methyltransferase and dopamine beta-hydroxylase, and the dexamethasone suppression test (SDT) did not show any biological marker value for outpatients even though both enzymes were determined to have hereditability. The HLA system, monoamine oxidase and acetylcholinesterase segregated differently from normal controls in samples of the patient population. The positive association findings with monoamine oxidase and the HLA system conflicted with the positive findings of other investigators, leaving doubtful their biological marker value. Red cell acetylcholinesterase was found to be significantly lower in affective disorder patients than in controls. This positive association finding was recently replicated by Mathews et al. (1982) but needs further confirmation. Using 28 blood group markers, a prior association study between the trait defining susceptibility to affective disorder and the genetic marker was positive for haptoglobin GC, and properdinfactor B, confirming earlier findings. Using the sib-pair method on the remaining 25 blood groups revealed that none other than peptidase A showed significant linkage with affective disorder since one significant finding is expected by chance. We conclude from the overall morbid risk data and segregation analyses that bipolar manic-depressive illness is a spectrum disease inherited through a multifactorial mode of genetic transmission (which is not synonymous with polygenetic inheritance) with possible genetic heterogeneity and find no evidence for X-linkage. Additional studies with acetylcholinesterase, haptoglobin, GC, and properdin-factor B are needed to confirm their positive biological/genetic marker value suggested by our long-term epidemiological study.
Structured interviews were used to study rates of past suicide attempts among 123 outpatients treated for affective disorders. Subjects met the Feighner criteria for major affective illness, and bipolar and unipolar groups were identified in accordance with the Fieve-Dunner criteria. Although a small group (N = 6), the women with a history of hospitalization for depression and outpatient treatment for hypomania (BP II) had the highest rate of past suicide attempts. (66 percent). This confirms previous findings. Women showed higher rates overall (39 percent vs. 28 percent for men). Suicide attempters were found to be significantly younger than nonattempters, which is in line with previous reports that suicide risk is high early in the course of bipolar illness. A trend for attempters to have received their first treatment at a younger age suggests that early onset may be a risk factor. No differences in marital status were found between attempters and nonattempters. Males and females did not differ in number, seriousness, or lethality of attempts.
Eighty-nine bipolar I patients were given a structured interview, the Schedule for Affective Disorders and Schizophrenia. Those who had experienced delusions or hallucinations at some time during the course of their illness were designated "psychotic," and those who had not were designated "nonpsychotic." The two groups were compared with regard to a number of outcome variables as well as age, age at first treatment, and duration of illness. The psychotic group had significantly poorer outcome in terms of social functioning. Although age, age at first treatment, and duration of illness distinguished between the two groups of patients, statistical analyses indicated that these variables did not account for differences in social outcome.
The authors rated 71 bipolar I patients on the basis of the number of different psychotic symptoms experienced during the course of their illness. Patients who became ill at a young age had significantly higher scores than patients with a later onset.
In contrast to a recently published report by Amsterdam and associates, the authors noted a higher frequency of abnormal dexamethasone suppression test results in 88 outpatients with primary depression (particularly the endogenous subtype) than in 49 normal controls.
Thirty-one children (age range, 7-14 years) of 18 probands with a bipolar disorder according to Research Diagnostic Criteria were assessed on clinical and psychological measures and compared with 18 matched normal control children. The authors found higher rates of childhood psychopathology in the children of the probands than in the control children. In addition, the experimental group was characterized by 1) a pattern on the WISC-R of higher verbal than performance IQs, 2) higher ratios of color to movement determinants on the Rorschach test, and 3) an overrepresentation of left-handedness. The implications of these findings are briefly discussed.
Patients taking lithium had a slightly higher serum creatinine concentration than controls. Creatinine concentration was independent of lithium level or therapy length, suggesting that lithium decreases glomerular filtration but that this effect is small, noncumulative, and of marginal clinical significance.
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The body composition of three unipolar and 17 bipolar patients, studied during the depressive state, was compared with that of 48 controls. The ratio of extracellular to intracellular water content was significantly less in male patients than in male controls: the difference between female patients and female controls was not statistically significant. In patients of both sexes, residual sodium concentration was greater in patients than in controls. The intracellular content of potassium was the same in patients as in controls. In six patients, body composition was studied prior to lithium carbonate therapy, after 17 days of treatment, and 17 days after discontinuing administration of the drug. The significant changes were a decrease in body weight during therapy, and a decrease in body water content and an increase in residual sodium concentration after drug treatment was discontinued.
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Red blood cell (RBC) glycine levels were examined in 27 bipolar patients, treated with lithium carbonate for a minimum of 8 months, who were either hypomanic, depressed, or euthymic in their mood. We found no difference in the RBC glycine or in the RBC: plasma glycine ratio between the hypomanic, depressed, or euthymic patients (P less than 0.1). There were statistically significant differences in RBC glycine levels in lithium-treated euthymic patients and normal controls. There was a strong positive correlation between serum lithium levels and both RBC glycine levels and the RBC: plasma glycine ratio.
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The age of onset of affective illness as measured by the initial psychiatric consultation for four affective subtypes was evaluated. Bipolar I (mean age = 28.00) and cyclothymics (mean age = 27.58) sought psychiatric consultation for their affective symptoms significantly earlier than unipolar patients (mean age = 34.69). Bipolar II patients (mean age = 31.54) sought psychiatric consultation at an age intermediate between bipolar I and unipolar patients. Male bipolar II patients sought psychiatric treatment significantly later than female bipolar II patients and there was a nonsignificant trend toward male cyclothymics initially seeking treatment later than female cyclothymics. In all, the range of age of onset for the four affective subtypes was quite wide suggesting that a patient was at risk for developing an affective disorder at any time from adolescence to the geriatric age range.