Biomedical subjects
Publications and source records attributed to G Winokur.
Prevalence of hallucinations and delusions was studied in 1,763 patients with unipolar major depression, bipolar affective disorder, and schizoaffective disorder. The authors found that the presence of psychotic features was negatively associated with age of onset for the group as a whole, and bipolar affective disorder (manic or mixed type) specifically. The clinical implications of the findings are discussed.
OBJECTIVE: Anxiety symptoms often appear within depressive episodes, but their significance is uncertain. This study sought to determine whether they indicate the coexistence of a separate disease process and whether they have prognostic significance. METHOD: A series of patients with primary depression who entered a follow-up and family study included 37 who also had obsessions or compulsions, 93 who had panic attacks, 101 who had phobias, and 196 who had none of these anxiety syndromes. Each of the overlapping groups defined by the presence of a specific anxiety syndrome was compared to the group that had none of these syndromes with respect to baseline demographic, phenomenological, and historical features, illness rates among directly interviewed relatives, and diagnostic stability and clinical outcome at semiannual follow-ups over a period of 5 years. RESULTS: Depressive symptoms at intake were more longstanding and severe among patients with specific anxiety symptoms, and these patients went on to experience more depressive morbidity during the ensuing 5 years. The development of autonomous anxiety disorders was rare, however, and specific anxiety syndromes in the probands did not increase risks for the corresponding disorders among relatives. CONCLUSIONS: When restricted to episodes of major depression, anxiety syndromes appear to be prognostically significant epiphenomena rather than indicators of an additional disorder.
Stepwise multiple logistic regression was utilized in an attempt to develop a statistical model that would predict suicide in a group of 1906 Iowans with affective disorders admitted to a tertiary care hospital. The risk factors identified by this approach included the number of prior suicide attempts, suicidal ideation on admission, bipolar affective disorder (manic or mixed type), gender, outcome at discharge, and unipolar depressive disorder in individuals with a family history of mania. However, the model failed to identify any of the patients who committed suicide. The results appear to support the contention that, based on present knowledge, it is not possible to predict suicide, even among a high-risk group of inpatients.
Stepwise multiple logistic regression was used in an attempt to develop a statistical model which would predict "recovery" in a group of 1471 depressives admitted to a tertiary care hospital. Six variables identified by this approach included: Electroconvulsive therapy, personality disorder, chronicity, anxiety disorder, organic mental disorder, and dysthymia. The meaning and significance of the findings are discussed.
OBJECTIVE: Some studies have suggested relationships between depression in probands and alcoholism in relatives. Other studies have not, but some of these have used inappropriate control groups or failed to divide probands by sex. METHOD: The present study controlled for sex of probands and used several comparison groups to further explore the familial relationship between depression and alcoholism. Diagnoses for 723 directly interviewed relatives of 326 probands with primary unipolar depression were compared to diagnoses in 469 control subjects chosen by an acquaintanceship method to demographically resemble the relatives of affective disorder probands. Diagnoses in the uninterviewed relatives of both control and depressed subjects were used for comparisons as well. RESULTS: Results indicated higher rates of alcoholism in the families of depressed women but not in the families of depressed men. CONCLUSIONS: This familial association between alcoholism and depression may be the result of either genetic or environmental factors or an interaction between the two.
A prospective study of male in-patients over 55 years old who met Feighner criteria for non-bipolar depression was performed to determine if a previous history of alcoholism significantly influenced treatment or response to treatment. Among 58 subjects with complete follow-up information, the 16 who had a history of alcoholism had a presentation at index which differed from that of the non-alcoholics, and on follow-up they clearly had more chronic illness. This elderly sample with alcoholism resembles 'neurotic-reactive' depressives described in younger samples, and supports a past history of alcoholism as being a risk factor for chronicity of depression on follow-up in the elderly population.
Unipolar depression and alcoholism were tested for genetic linkage to esterase-D at 13q14.1. Tight linkage to esterase-D was ruled out for three phenotypes using three models of penetrance: (1) unipolar depression and alcoholism taken together as affected, (2) unipolar depression alone as affected with alcoholism considered unaffected and (3) alcoholism alone as affected with unipolar depression considered unaffected. This study does not support an earlier finding of possible linkage between the esterase-D locus at 13q14.1 and alcoholism.
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Eighteen families informative for c-Harvey-ras-1 and INS DNA markers were tested for linkage to unipolar depression and alcoholism. No evidence of linkage was found between these DNA markers and the disorders observed in the families. This study fails to replicate the Old Order Amish Study and suggests that a significant degree of genetic heterogeneity may be present among psychiatric disorders.
Bipolars treated with electroconvulsive therapy (ECT) during the index episode were matched on the variables of age, sex, previous admissions and previous hospitalizations with 23 bipolars who did not receive ECT. A similar match was made for 42 unipolars who were under the age of 40 at time of admission. All patients were followed for 5 years. Those patients treated with ECT, both bipolars and unipolars, had the same numbers of episodes in follow-up as their matched groups. However, in both bipolar and unipolar ECT-treated patients, there were more follow-up rehospitalizations. The reason for this is not known but three possibilities exist. Successful treatment with ECT may make the family and patient more prone to consider rehospitalization. Secondly, the originally treated ECT patients may have had more aggressive doctors who were more likely to rehospitalize. Finally, ECT may change the course of an individual's illness in such a way that more severe episodes occur and rehospitalizations are necessary. The findings suggest the need for long-term studies following ECT on clinical and biological variables.
Based on evidence available at present, it appears that heterogeneity does exist within bipolar disorder. Persons with mania differ in family history of affective illness, their age at the onset of illness, sex, and organic cause and course of the illness. The question of how these variables influence an individual's response to treatment has never been systematically studied. Multicenter trials of the various antimanic agents need to be conducted to determine whether the various subgroups of manic patients have different pharmacological response profiles. At present, the clinical management of mania is best approached using lithium carbonate in a dosage adequate to achieve a 12-hour serum lithium level to 1.0 to 1.2 mEq/L. The time to response is usually 2 to 3 weeks, and during this period an antipsychotic or benzodiazepine agent may be added to help control symptoms such as agitation or sleeplessness. Prophylactic maintenance with 12-hour serum lithium levels between 0.8 and 1.0 mEq/L should be used for at least 6 to 12 months after resolution of the manic episode. In patients with more than one episode, lithium maintenance therapy may need to be continued indefinitely. In patients who are not responsive to lithium, the most prominent alternative therapies include anticonvulsants and calcium-channel blocking agents. Anticonvulsants (e.g., carbamazepine, valproic acid, clonazepam) are generally first used as alternative therapy (either alone, or in combination with lithium), followed by a calcium-channel blocker (e.g., verapamil). Clinical practice would generally suggest first using the alternative agent alone, then adding lithium if response is inadequate.(ABSTRACT TRUNCATED AT 250 WORDS)
The data suggest that the primary/secondary concept is more appropriate than the concept of comorbidity. This is based on the fact that many psychiatric illnesses have very high frequencies of depression associated with them, far more than what would be considered expected by chance. The secondary concept is important in that it has considerable clinical meaning and is a way to predict response to treatment and course after the patient is seen by a clinician.
The influence of age on the natural history of unipolar depression when treated with electroconvulsive therapy (ECT) was studied using a naturalistic/archival study design. A sample of 125 patients who received no somatic treatment were compared with 128 patients who all received a course of ECT with at least four treatments. Patients were separated according to age at admission. Treated patients, aged 40 or older, who were clearly remitters showed no differences in previous episodes, subsequent episodes, subsequent hospitalizations, or likelihood of experiencing a period of full recovery when compared with a similar group of untreated patients. Hospitalization greater than 1 year and chronicity were significantly more common in the untreated older subjects. Treated patients aged 39 or younger, who also were clearly remitters, showed significant increases in subsequent episodes and subsequent hospitalizations when compared with a group of depressed patients of similar age who received no somatic treatment. Hospitalization greater than 1 year was also more common in the untreated younger patients. ECT clearly reduces the rate of chronicity in older patients but may be associated with an increase in episodes after treatment in the younger population.
As part of a study of the possible subgroups of unipolar affective disease, 27 families were ascertained as depression spectrum disease (DSD) families. The purpose of this study was an investigation of the linkage relationships between DSD and 30 genetic markers using the robust sib-pair and lod-score methods. Using the sib-pair methods, evidence for linkage was found with orosomucoid (ORM) on chromosome 9q (p = 0.006), regardless of whether only individuals with unipolar depression, alcoholism, or antisocial personality were considered to be affected, or whether individuals with any psychiatric disorder were considered to be affected. Weak evidence of linkage with ORM was corroborated using lod-score methods when a narrow definition of depression spectrum disease was used, although stronger evidence of linkage was found with ORM when any psychiatric disorder was considered to be affected. The maximum lod-score for ORM was 1.68 at a male recombination fraction of 0.23 and a female recombination fraction of 0.01.
In a study of the subgroups of unipolar affective disease, 13 families were ascertained as pure depressive disease (PDD) families. Here we investigate linkage relationships between PDD and 30 genetic markers in these families. Using the robust sib-pair method of linkage analysis, evidence for possible linkage or association was found with five loci: the ABO and MNS blood groups, immunoglobulin kappa (IGK), proline rich parotid salivary protein (PR) and glyoxylase-1 (GLO1). Weak evidence of linkage with ABO was supported using the lod score method of analysis. The maximum lod score between PDD and ABO was 1.42 at a male recombination fraction of 0.09 and a female recombination fraction of 0.03. When these results from the sib-pair analysis were combined with the results from two previous sib-pair studies on PDD, the ABO, MNS and IGK loci were found to be significant (P = 0.05, P = 0.005, P = 0.05, respectively, not allowing for multiple tests).
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The effectiveness of fluoxetine as an antidepressant was contrasted with trazodone in a 6-week double-blind trial in 40 patients. The total score on the Hamilton Rating Scale for Depression and the global improvement score on the Clinical Global Impressions scale favored trazodone at the end of 3 weeks of treatment. However, that difference was no longer apparent during the remainder of the study. The authors hypothesize that fluoxetine 20 mg/day may be an ineffective dosage of the drug or that fluoxetine has a slower onset of antidepressant action than does trazodone.
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