Polarity sequence, depression, and chronicity in bipolar I disorder

Five independent studies show that polarity sequence is associated with prognosis in bipolar I disorder. Episodes in which major depression precedes mania (DMI) lead to higher morbidity than biphasic episodes which begin with mania (MDI). However, little is known about the prognostic significance of polarity sequence for long-term outcome. This study examined polarity sequence across multiple episodes among 165 bipolar I patients followed prospectively for up to 15 years as part of the NIMH Collaborative Study of Depression. Episodes beginning with major depression were significantly longer than those beginning with mania for the first three prospectively observed episodes when pooling all episode types-monophasic, biphasic, and polyphasic. Furthermore, affective polarity at onset for the first prospectively observed episode was associated with polarity at onset for the remaining three episodes. Patients whose first prospectively observed episode began with depression had higher overall morbidity during the entire follow-up period.     

The significance of psychotic features in manic episodes: a report from the NIMH collaborative study

BACKGROUND: Psychotic features in the context of major depressive syndromes have correlates in symptom severity, acute treatment response and long-term prognosis. Little is known as to whether psychotic features have similar importance when they occur within manic syndromes. METHODS: These data derive from a multi-center, long-term follow-up of patients with major affective disorder. Raters conducted follow-up interviews at 6-month intervals for the first 5 years and annually thereafter. A sub-set of probands participated in a family study in which all available, adult, first-degree relatives were interviewed as well. RESULTS: Of 139 who entered the study in an episode of mania, 90 patients had psychotic features. Symptom severity ratings at intake were more severe for this group. Though time to first recovery and time to first relapse did not distinguish the groups, psychotic features were associated with a greater number of weeks ill during follow-up and the strength of this association was similar to that seen for psychotic features within depressed patients described in an earlier publication. Patients with psychotic mania at intake did not differ significantly from those with nonpsychotic mania by response to acute lithium treatment, suicidal behavior during follow-up, or risks for affective disorder among first-degree relatives. Psychotic features within manic syndromes were not associated with high psychosis ratings during follow-up. In contrast, when psychotic features accompanied depressive syndromes, they strongly predicted the number of weeks with psychosis during follow-up, particularly among individuals whose episodes at intake were less acute. CONCLUSIONS: As with major depressive syndromes, psychotic features in mania are associated with greater symptom severity and higher morbidity in the long-term. Psychotic features are much less predictive of future psychosis when they occur within a manic syndrome than when they occur within a depressive syndrome.     

Bipolar I affective disorder: predictors of outcome after 15 years

Background: Robust predictors of long-term outcome in bipolar affective disorder would have substantial importance to both clinicians and researchers. Such predictors are not available, however, perhaps because of the limitations of previous efforts to find them. Methods: In this study, 113 patients with bipolar affective disorder were followed semiannually for 5 years and annually for a subsequent 15 years. Of these, 23 (20.4%) had a poor long-term outcome indicated by the presence of mania or major depressive disorder throughout the 15th year. Results: Among the baseline demographic and clinical variables tested, only active alcoholism and low levels of optimum functioning in the preceding 5 years characterized poor outcome patients. The persistence of depressive symptoms in the first 2 years of follow-up predicted depressive symptoms 15 years later but the early persistence of manic symptoms seemed to have no predictive value. A regression analysis eliminated alcoholism as an independent predictor. Thus, only poor optimal functioning in the 5 years before baseline assessment, and the persistence of depressive symptoms in the two subsequent years, were independently associated with poor, long-term prognosis. Limitations: Patients were recruited at tertiary care centers and sampling was therefore biased toward greater severity and chronicity. As is true of all naturalistic studies of course, treatment was not controlled. Conclusion: These findings suggest the existence of a poor outcome, depression-prone subtype of bipolar affective disorder.     

Polymorphism of adhesion molecule CD31 is not a significant risk factor for graft-versus-host disease

Mismatch between bone marrow transplant (BMT) patient and donor for an amino acid polymorphism within the adhesion molecule CD31 has recently been reported to increase risk for the development of graft-versus-host disease (GVHD). We further examined this association in a larger series of 301 BMT patients (227 with grade III/IV GVHD and 74 with grade 0 GVHD) and their HLA-identical sibling donors. CD31 genotypes were determined by polymerase chain reaction and restriction endonuclease digestion. The role of mismatch at the CD31 locus in the development of GVHD was assessed by analyzing the extent of CD31 identity and CD31 compatibility among the grade 0 GVHD and grade III/IV GVHD sibling pairs. No significant association between CD31 mismatch and the development of severe GVHD was detected in our overall patient population. Sixty-three percent of grade III/IV GVHD sibling pairs and 69% of grade 0 GVHD sibling pairs had CD31 genotypes that were identical (P = .36, odds ratio = 1.30). In addition, neither the grade 0 GVHD group (P = .10) nor the grade III/IV GVHD group (P = .27) differed significantly from the expected probability of identity between sibling pairs. Mismatch at the CD31 polymorphism between recipients and donors showed no consistent association with the development of GVHD. Current evidence does not support the value of CD31 mismatch in the selection of BMT donors.     

Validity of an operational definition for neurotic unipolar major depression

After we reviewed the literature to identify the clinical and phenomenologic correlates of neurotic depression, we constructed a 6-item operational definition to distinguish neurotic unipolar major depressive disorder from non-neurotic major depression. The neurotic depressives were characterized by a low rate of abnormal dexamethasone suppression test (DST) results and a strong family history of alcoholism. Neurotic depressives improved less than non-neurotic depressives during the index hospitalization, and were more frequently rehospitalized during a 6-month prospective follow-up. Neurotic subtyping was significantly negatively associated with DSM-III melancholia. Neurotic classification remained significantly associated with the above validating variables after melancholic status was held constant, whereas melancholic subtyping did not predict DST results, familial alcoholism rates, or outcome when neurotic status was controlled.     

Uranyl acetate induces hprt mutations and uranium-DNA adducts in Chinese hamster ovary EM9 cells

Questions about possible adverse health effects from exposures to uranium have arisen as a result of uranium mining, residual mine tailings and use of depleted uranium in the military. The purpose of the current study was to measure the toxicity of depleted uranium as uranyl acetate (UA) in mammalian cells. The activity of UA in the parental CHO AA8 line was compared with that in the XRCC1-deficient CHO EM9 line. Cytotoxicity was measured by clonogenic survival. A dose of 200 microM UA over 24 h produced 3.1-fold greater cell death in the CHO EM9 than the CHO AA8 line, and a dose of 300 microM was 1.7-fold more cytotoxic. Mutagenicity at the hypoxanthine (guanine) phosphoribosyltransferase (hprt) locus was measured by selection with 6-thioguanine. A dose of 200 microM UA produced approximately 5-fold higher averaged induced mutant frequency in the CHO EM9 line relative to the CHO AA8 line. The generation of DNA strand breaks was measured by the alkaline comet assay at 40 min and 24 h exposures. DNA strand breaks were detected in both lines; however a dose response may have been masked by U-DNA adducts or crosslinks. Uranium-DNA adducts were measured by inductively coupled plasma optical emission spectroscopy (ICP-OES) at 24 and 48 h exposures. A maximum adduct level of 8 U atoms/10(3) DNA-P for the 300 microM dose was found in the EM9 line after 48 h. This is the first report of the formation of uranium-DNA adducts and mutations in mammalian cells after direct exposure to a depleted uranium compound. Data suggest that uranium could be chemically genotoxic and mutagenic through the formation of strand breaks and covalent U-DNA adducts. Thus the health risks for uranium exposure could go beyond those for radiation exposure.