The prevalence and disability of bipolar spectrum disorders in the US population: re-analysis of the ECA database taking into account subthreshold cases

BACKGROUND: Despite emerging international consensus on the high prevalence of the bipolar spectrum in both clinical and community samples, many skeptics contend that narrowly defined bipolar disorder with a lifetime rate of about 1% represents a more accurate estimate of prevalence. This may in part be due to the fact that higher figures proposed for the bipolar spectrum (5-8%) have not been based on national data and have not included all levels of manic symptom severity. In the present secondary analyses of the US National Epidemiological Catchment Area (ECA) database, we provide further clarification on this fundamental public health issue. METHODS: All respondents in the first wave (first interview) of the ECA household five site sample (n=18252) were classified on the basis of DSM-III criteria into lifetime manic and hypomanic episodes, as well as those with at least two lifetime manic/hypomanic symptoms below the threshold for at least 1 week duration (subsyndromal manic symptoms [SSM] group). Odds ratios were calculated on lifetime service utilization for mental health problems, measures of adverse psychosocial outcome, and suicidal behavior compared to subjects with no mental disorders or manic symptoms. RESULTS: As originally reported nearly two decades ago by the primary investigators of the ECA, the lifetime prevalence for manic episode was 0.8%, and for hypomania, 0.5%. What is new here is the inclusion of subthreshold SSM subjects, which accounted for 5.1%, yielding a total of 6.4% lifetime prevalence for the bipolar spectrum. All three (manic, hypomanic and SSM) groups had greater marital disruption. There were significant increases in lifetime health service utilization, need for welfare and disability benefits and suicidal behavior when the SSM, hypomanic and manic subjects were compared to the no mental disorder group. Suicidal behavior was non-significantly highest in the hypomanic (bipolar II) group. Otherwise, hypomanic and manic groups had comparable level of service utilization and social disruption. LIMITATIONS: Comorbid disorders, which might influence functioning, were not included in the present analyses. CONCLUSION: These secondary analyses of the US National ECA database provide convincing evidence for the high prevalence of a spectrum of bipolarity in the community at 6.4%, and indicate that subthreshold cases are at least five times more prevalent than DSM-based core syndromal diagnoses at about 1%. These SSM subjects, who met the criteria of "caseness" from the point of view of harmful dysfunction, are of great theoretical and public health significance.     

The gel test: use in the identification of unexpected antibodies to blood group antigens

The IgG GEL test was compared with the LISS tube test (L?w and Messeter's low-ionic-strength saline) for antibody identification. The suitability of red blood cells (RBCs) pretreated with ficin, dithiothreitol (DTT), or chloroquine diphosphate (CDP) also was assessed for use in the GEL test. In addition, time-in-motion studies were performed comparing GEL (12 panels per batch) with polyethylene glycol (PEG) tube tests (3 panels per batch). In 57 antibody identification studies, there were 63 GEL+ LISS+, 2 GEL+ LISS-, and 6 GEL-LISS+ antibodies. Among the GEL+ LISS+ antibodies were 19 that yielded stronger reactions in GEL than in LISS; by virtue of their specificity, 14 of these are considered potentially significant: D, 5 E, 2 e, 2 Jka, 2 S, K, and Fya. There were 38 antibodies that yielded equivalent results by both methods, including 31 that are considered potentially significant. Of six antibodies with significantly greater reactivity in LISS, there were three anti-Rh and three that are considered harmless with respect to transfusion management. The two GEL+ LISS- antibodies (anti-Jkb) were potentially significant. GEL- LISS+ reactions involved only harmless antibodies. Of the 50 antibodies of potential significance, GEL yielded equivalent or superior results in 47 (94%) instances. Additionally, GEL failed to detect 6 of 21 harmless antibodies. Expected results were obtained with normal serum or plasma and antibodies of known specificity in tests with RBCs treated with ficin, DTT, or CDP. Hands-on-time required for each GEL panel was 2 to 21/2 minutes compared with 12 minutes for PEG. These data document the suitability of GEL for use in antibody identification studies.     

PEG adsorption of autoantibodies causes loss of concomitant alloantibody

Use of polyethylene glycol (PEG) to promote adsorption of autoantibodies is reported to give good recovery of concomitant alloantibodies. In initial experiments, PEG and ZZAP (Ficin and DTT) adsorption procedures were compared for removal of autoantibody and recovery of alloantibody. Postadsorption studies (n = 11) were performed and hemagglutination scores compared. In subsequent studies, equal volumes of alloantibody containing sera, PEG, and antigen-negative red blood cells (RBCs) were used in twofold adsorption experiments. Saline was substituted for PEG for control purposes. Postadsorption titers and immunoglobulin levels were determined. Autoantibodies were completely removed by both methods (n = 5); better by PEG (n = 3); better by ZZAP (n = 1); and not adsorbed (n = 1), and partially adsorbed by both (n = 1). Alloantibody recovery was comparable in three cases (E, K, Jka) but weaker by at least one reaction grade in four (K,E, Jka, and antibody to low-frequency antigen). The latter anti-Jka reacted 1+ with Jk(a+b+) RBCs after ZZAP adsorption but was nonreactive with the same RBCs following PEG adsorption. Titers of six alloantibodies adsorbed with antigen-negative RBCs in PEG were markedly weaker (range 2 to 8) compared to saline controls (range 4 to 32). IgG levels for PEG adsorbed (range 128 to 243 mg/dL) were 50% lower than controls (range 265 to 505 mg/dL). Although PEG adsorption is effective in removing autoantibody, the precipitation of immunoglobulin by PEG may result in failure to detect underlying alloantibody.     

Interaction of human plasma fibronectin with cariogenic and non-cariogenic oral streptococci

The interaction of purified human plasma fibronectin (Fn) with bacteria was studied with a variety of oral streptococci. Each of the strains of Streptococcus mutans, Streptococcus salivarius, Streptococcus sanguis, and Streptococcus mitis tested was aggregated by Fn to various degrees, depending on the concentration of Fn added to the test mixtures. Binding assays performed with radiolabeled Fn and various strains of streptococci demonstrated various capabilities to bind Fn, and the amount of Fn bound by each strain was paralleled by its Fn-induced aggregation, with S. mutans 6715 giving the highest values in both assays. Because of the avid binding of Fn by certain strains of potentially cariogenic streptococci, we investigated the possibility that Fn may be present in human saliva and may be adsorbed from saliva onto artificial tooth pellicles. Immunoreactive Fn was detected in paraffin-stimulated whole saliva by enzyme-linked immunosorbent assays of saliva adsorbed onto gelatin-coated cuvettes and by immunoelectroblots (Western blots) of salivary components separated on sodium dodecyl sulfate-polyacrylamide slab gels. Furthermore, immunoreactive Fn was found to be present in artificial tooth pellicles formed by incubating hydroxyapatite beads with whole human saliva. These results demonstrate that certain strains of oral streptococci bind to and are aggregated by Fn. The presence of Fn in artificial tooth pellicles suggests that this macromolecule may play a role in the attachment of potentially cariogenic and other oral streptococci to dental tissues.     

Hypoesthesia after anterior cruciate ligament reconstruction: The relationship between proprioception and vibration perception deficits in individuals greater than one year post-surgery

Background

While surgical reconstruction restores mechanical stability following anterior cruciate ligament (ACL) rupture, many experience early-onset osteoarthritis despite surgery. Neurophysiological changes are hypothesized to contribute to knee osteoarthritis progression. Proprioceptive deficits have been reported following ACL injury/reconstruction; however, vibration perception threshold (VPT) has been less studied. This study explored relationships between pain, VPT, proprioception, function, and strength following ACL-reconstruction.

In vitro effector activity of Pneumocystis murina-specific T-cytotoxic-1 CD8+ T cells: role of granulocyte-macrophage colony-stimulating factor

Human immunodeficiency virus (HIV)-related opportunistic infections continue to occur in patients who are newly diagnosed with HIV infection, those in the early course of highly active antiretroviral therapy or nonadherent to HIV care, and other immunosuppressed individuals. One of the most common opportunistic infections in these patients is Pneumocystis pneumonia. CD8+ T cells are recruited to the lung after P. carinii infection and have been associated with both lung injury and host defense. This variability may be due to subpopulations of CD8+ T cells recruited to the lung. We have previously shown using adoptive transfer studies that in vivo-generated T-cytotoxic-1 (Tc1) CD8+ T cells, defined by the secretion of gamma interferon (IFN-gamma), have effector activity against Pneumocystis spp. in vitro as well as in vivo. To better understand the mechanisms of these effects, we generated, expanded, and tested Tc1 and Tc2 CD8+ T cells specific for P. murina ex vivo. Tc1-polarized CD8+ T cells secreted higher levels of IFN-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) and lower levels of interleukin-4 (IL-4), IL-5, IL-10, and IL-13 than Tc2 CD8+ T cells when stimulated with P. murina antigen. Moreover, Tc1 CD8+ T cells demonstrated enhanced effector activity in a macrophage-mediated killing assay which was independent of cell contact. The augmentation in macrophage-mediated P. murina killing was significantly abrogated when GM-CSF was neutralized in the Tc1 CD8+ T cells. These data support the possibility that antigen-specific GM-CSF secretion is critical for effector activity of P. murina-specific Tc1 CD8+ T cells in vitro.     

Requirements for autoimmune responses to mouse gastric autoantigens

Autoimmune gastritis, in which the H+/K(+)-ATPase of parietal cells is the major antigen, is one of the most common autoimmune diseases. Here we examined if specific properties of the H+/K(+)-ATPase or parietal cells are involved in rendering them autoimmune targets. The model antigens beta-galactosidase and ovalbumin (OVA) were expressed in parietal cells of transgenic mice. On experimental induction of autoimmune gastritis by neonatal thymectomy, autoantibodies to beta-galactosidase developed in mice expressing beta-galactosidase in parietal cells, a response that was independent of either the response to the gastric H+/K(+)-ATPase or gastric inflammation. In contrast, mice that expressed OVA in parietal cells did not exhibit an antibody response to OVA after thymectomy. However, increasing the frequency of anti-OVA T lymphocytes in OVA-expressing mice resulted in autoantibodies to OVA and gastritis. These studies indicate that parietal cells can present a variety of antigens to the immune system. Factors such as the identity and expression level of the autoantigen and the frequency of autoreactive T cells play a role in determining the prevalence and outcome of the particular immune response. In addition, as not all mice of a particular genotype displayed autoimmunity, random events are involved in determining the target of autoimmune recognition.