The significance of past mania or hypomania in the course and outcome of major depression

Patients with primary major depression (N = 372) were followed for 2 years to determine the prognostic importance of past manic or hypomanic episodes. While bipolar I and bipolar II patients were more likely to relapse and bipolar I patients were more likely to attempt suicide, these patients resembled nonbipolar depressed patients in likelihood of recovery and psychosocial impairment in various areas. Compared to nonbipolar patients, those with bipolar I depression were much more likely to develop mania, while bipolar II patients were more likely to develop hypomania. Cycling during the index episode predicted a relatively low likelihood of recovery for bipolar I patients but had no apparent prognostic significance for patients with bipolar II illness.     

Diagnosis of schizophrenia. Prediction of short-term outcome

Seven systems for the diagnosis of schizophrenia were compared in their ability to predict short-term outcome at follow-up: with each other, with selected specific symptoms, and with a simple additive composite symptom score. None of the systems nor the symptoms predicted strongly, but DSM-III and Schneiderian First Rank Symptoms and the composite score performed somewhat better than the other predictors.     

Stability of psychiatric diagnoses. An application to the affective disorders.

In the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression study, data were collected on 2226 first-degree relatives of 612 probands. A second, "blind" reassessment of all relatives was attempted 6 years after the initial evaluation. We report on a final sample of 1629 relatives assessed twice using the Schedule for Affective Disorders and Schizophrenia-Lifetime version. We summarize methods for using stability of diagnosis to model the relationship between clinical covariates and the probability of being a true case. Moreover, we define an index of caseness that can be used to narrow the criteria for who is a case. Of those positive for major depressive disorder at initial evaluation, 74% were positive (on a lifetime basis) at follow-up (ie, were stable). There is a gradient: 48% of those who had three symptoms and no treatment were stable, compared with 96% of those with eight symptoms and treatment. For major depressive disorder, we found the caseness index for those with lifetime mania more severe than that of nonbipolar patients, with those who had hypomania being intermediate. A hierarchical analysis indicated that bipolar I tends to be diagnosed as schizoaffective-manic across occasions, and vice versa. This is consistent with the prior familial analyses that suggest these two diagnoses be combined into a single bipolar phenotype. The analysis for major depressive disorder indicates that caseness appears to represent quantitative, rather than qualitative, differences, with no natural cutoff to identify distinct subgroups. Finally, we discuss implications including utility in genetic analyses, estimation of incidence or prevalence allowing for diagnostic error, and examination of cohort effects.     

Relationship between premenstrual symptoms and general well-being

Data on the general well-being and premenstrual symptoms of military wives were collected on two occasions one year apart. The women's general well-being and premenstrual symptoms were highly correlated on both occasions, but an even higher correlation was found between the presence of premenstrual symptoms at time 1 and the presence of premenstrual symptoms at time 2. Further analyses revealed that women with higher scores on general well-being and premenstrual symptoms were older and reported fewer cognitive depressive symptoms than women with lower scores on general well-being and premenstrual symptoms. At the one-year follow-up, the women with lower scores on general well-being who complained of premenstrual symptoms were more depressed than those who did not.     

A follow-up linkage study supports evidence for a bipolar affective disorder locus on chromosome 21q22

Evidence for linkage between bipolar affective disorder (BP) and 21q22 was first reported by our group in a single large pedigree with a lod score of 3.41 with the PFKL locus. In a subsequent study, with denser marker coverage in 40 multiplex BP pedigrees, we reported supporting evidence with a two-point lod score of 2.76 at the D21S1260 locus, about 6 cM proximal to PFKL. For cost-efficiency, the individuals genotyped in that study comprised a subset of our large pedigree sample. To augment our previous analysis, we now report a follow-up study including a larger sample set with an additional 331 typed individuals from the original 40 families, improved marker coverage, and an additional 16 pedigrees. The analysis of all 56 pedigrees (a total of 862 genotyped individuals vs. the 372 genotyped previously), the largest multigenerational BP pedigree sample reportedly analyzed to date, supports our previous results, with a two-point lod score of 3.56 with D21S1260. The 16 new pedigrees analyzed separately gave a maximum two-point lod score of 1.89 at D21S266, less than 1 cM proximal to D21S1260. Our results are consistent with a putative BP locus on 21q22.     

Alcoholism and drug abuse in three groups — bipolar I, unipolars and their acquaintances

Objective: Previous work has shown that manic-depressive illness and alcohol abuse are linked. This study further explores the relationship of alcohol and drug abuse in bipolar I patients and unipolar depressives and a comparison group obtained through the acquaintance method. Method: Diagnosis was accomplished according to Research Diagnostic Criteria (RDC): controls=469; bipolars=277; unipolar depressives=678. Systematic data were gathered using the SADS on lifetime and current drug abuse and alcoholism. Both patients and comparison subjects were then followed prospectively for 10 years. First degree family members were interviewed using the RDC family history method. Results: The group of bipolar patients and the group of unipolar patients had higher rates of drug and alcohol abuse than the comparison group when primary and secondary affective disorder patients were combined. However, primary unipolar patients did not have higher rates of alcohol or drug abuse than the comparison group. In contrast, primary bipolar patients had higher rates of alcoholism, stimulant abuse, and ever having abused a drug than the primary unipolar group and the control group. In an evaluation of the bipolar patients, drug abusers were significantly younger at intake and had a significantly younger age of onset of bipolar disorder. There was a significant increase in family history of mania or schizoaffective mania in the drug-abusing bipolar patients as compared to the non-abusing bipolar patients. Limitation: As in all adult samples of patients with affective illness, the chronology of alcohol and substance problems vis-à-vis the onset of illness was determined retrospectively. Conclusions: (1) Alcoholism and drug abuse are more frequent in bipolar than unipolar patients. (2) The drug abuse of bipolar patients tends toward the abuse of stimulant drugs. (3) In a bipolar patient, familial diathesis for mania is significantly associated with the abuse of alcohol and drugs. (4) More provocatively, these findings suggest the hypothesis of a common familial-genetic diathesis for a subtype of bipolar I, alcohol and stimulant abuse. Clinical implications: The present analyses, coupled with two previous ones from the CDS, suggest that drug abuse may precipitate an earlier onset of bipolar I disorder in those who already have a familial predisposition for mania. Furthermore, in dually diagnosed patients with manic-depressive and alcohol/stimulant abuse history, mood stabilization of the bipolar disorder represents a rational approach to control concurrent alcohol and drug problems, and should be studied in systematic controlled trials.     

Phenomenology and family history in DSM-III psychotic depression

Depressed inpatients with psychotic features were compared to those without them in terms of demographic features, depressive symptoms at intake and family history. These variables were then used to compare patients with mood-congruent psychotic features to those with mood-incongruent psychotic features. Patterns of familial psychopathology were similar for psychotic and non-psychotic patients. In accord with other studies, the families of mood-incongruent patients had slightly more schizophrenia and significantly less depression than did the families of mood-congruent patients. Depressive symptoms, particularly those used to define major depression and melancholia, were more severe in psychotic patients. Moreover, these particular depressive symptoms were more likely to distinguish mood-congruent from mood-incongruent patients than were other depressive symptoms. Thus mood-congruent psychotic features accompanied a more typical depressive syndrome than did mood-incongruent psychotic features.     

Course-related depressive syndromes in schizophrenia

The authors evaluated 20 patients, diagnosed by Research Diagnostic Criteria after 1 week of hospitalization as having schizophrenia, weekly throughout their hospitalization. Four patients developed syndromes of depression after resolution of their psychoses: three manifesting a "minor" and one a "major" postpsychotic depressive syndrome. Four other patients went on to develop syndromes equivalent to major depression at a time when they were still actively psychotic, and their cross-sectional diagnoses were therefore changed to schizoaffective disorder, depressed type. The authors discuss the implications of these findings for diagnosis.     

Chronic fatigue syndrome in private practice psychiatry: family history of physical and mental health

Forty-five psychiatric patients with chronic fatigue syndrome (CFS) were compared, using the case-control method, to two control groups selected from the same practice and matched on age, gender, and psychiatric diagnosis. The first control group (C-I, N=90) was selected on the basis of relatively good physical health. The second control group (C-II, N=45) was selected without regard to physical health. The reported family history of physical health revealed: the CFS mothers died at a younger age than the C-II mothers; both parents died before age 65 among the CFS parents more frequently than did the C-I parents; and the CFS parents had an increased prevalence of cancer, autoimmune disorders, and CFS-like conditions as compared to the families of one or both control groups. The reported family history of mental disorders revealed no significant differences in any of these conditions between the CFS patients and either control group.