Early clinical predictors and correlates of long-term morbidity in bipolar disorder

OBJECTIVES: Identifying factors predictive of long-term morbidity should improve clinical planning limiting disability and mortality associated with bipolar disorder (BD). METHODS: We analyzed factors associated with total, depressive and mania-related long-term morbidity and their ratio D/M, as %-time ill between a first-lifetime major affective episode and last follow-up of 207 BD subjects. Bivariate comparisons were followed by multivariable linear regression modeling. RESULTS: Total % of months ill during follow-up was greater in 96 BD-II (40.2%) than 111 BD-I subjects (28.4%; P=0.001). Time in depression averaged 26.1% in BD-II and 14.3% in BD-I, whereas mania-related morbidity was similar in both, averaging 13.9%. Their ratio D/M was 3.7-fold greater in BD-II than BD-I (5.74 vs. 1.96; P<0.0001). Predictive factors independently associated with total %-time ill were: [a] BD-II diagnosis, [b] longer prodrome from antecedents to first affective episode, and [c] any psychiatric comorbidity. Associated with %-time depressed were: [a] BD-II diagnosis, [b] any antecedent psychiatric syndrome, [c] psychiatric comorbidity, and [d] agitated/psychotic depressive first affective episode. Associated with %-time in mania-like illness were: [a] fewer years ill and [b] (hypo)manic first affective episode. The long-term D/M morbidity ratio was associated with: [a] anxious temperament, [b] depressive first episode, and [c] BD-II diagnosis. CONCLUSIONS: Long-term depressive greatly exceeded mania-like morbidity in BD patients. BD-II subjects spent 42% more time ill overall, with a 3.7-times greater D/M morbidity ratio, than BD-I. More time depressed was predicted by agitated/psychotic initial depressive episodes, psychiatric comorbidity, and BD-II diagnosis. Longer prodrome and any antecedent psychiatric syndrome were respectively associated with total and depressive morbidity

Finding benchmark brown dwarfs to probe the IMF as a function of time

Using a simulated disk brown dwarf (BD) population, we find that new large area infrared surveys are expected to identify enough BDs covering wide enough mass--age ranges to potentially measure the mass function down to ~0.03Mo, and the BD formation history out to 10 Gyr, at a level capable of establishing if BD formation follows star formation. We suggest these capabilities are best realised by spectroscopic calibration of BD properties (Teff, g and [M/H]) which, when combined with a measured luminosity and an evolutionary model can give BD mass and age relatively independent of BD atmosphere models. Such calibration requires an empirical understanding of how BD spectra are affected by variations in these properties, and thus the identification and study of "benchmark BDs" whose age and composition can be established independently. We identify the best sources of benchmark BDs as young open cluster members, moving group members, and wide (>1000AU) BD companions to both subgiant stars and high mass white dwarfs (WDs). We have used 2MASS to measure a wide L dwarf companion fraction of 2.7(+0.7/-0.5)%, which equates to a BD companion fraction of 34(+9/-6)% for an alpha~1 companion mass function. Using this value we simulate populations of wide BD binaries, and estimate that 80(+21/-14) subgiant--BD binaries, and 50(+13/-10) benchmark WD--BD binaries could be identified using current and new facilities. The WD--BD binaries should all be identifiable using the Large Area Survey component of UKIDSS combined with Sloan. Discovery of the subgiant--BD binaries will require a NIR imaging campaign around a large (~900) sample of Hipparcos subgiants. If identified, spectral studies of these benchmark brown dwarfs could reveal the spectral sensitivities across the Teff, g and [M/H] space probed by new surveys.Comment: 18 pages, 12 figures, accepted for publication in MNRA

Guillain-Barré Syndrome-related campylobacter jejuni in Bangladesh: ganglioside mimicry and cross-reactive antibodies

BACKGROUND: &lt;br/&gt; Campylobacter jejuni is the predominant antecedent infection in Guillain-Barré syndrome (GBS). Molecular mimicry and cross-reactive immune responses to C. jejuni lipo-oligosaccharides (LOS) precipitate the development of GBS, although this mechanism has not been established in patients from developing countries. We determined the carbohydrate mimicry between C. jejuni LOS and gangliosides, and the cross-reactive antibody response in patients with GBS in Bangladesh.&lt;br/&gt; METHODOLOGY:&lt;br/&gt; Sera from 97 GBS patients, and 120 neurological and family controls were tested for antibody reactivity against LOS from C. jejuni isolates from GBS patients in Bangladesh (BD-07, BD-39, BD-10, BD-67 and BD-94) by enzyme-linked immunosorbent assay (ELISA). Cross-reactivity to LOS was determined by ELISA. The LOS outer core structures of C. jejuni strains associated with GBS/MFS were determined by mass spectrometry.&lt;br/&gt; PRINCIPLE FINDINGS:&lt;br/&gt; IgG antibodies to LOS from C. jejuni BD-07, BD-39, BD-10, and BD-67 IgG antibodies were found in serum from 56%, 58%, 14% and 15% of GBS patients respectively, as compared to very low frequency (&#60;3%) in controls (p&#60;0.001). Monoclonal antibodies specific for GM1 and GD1a reacted strongly with LOS from the C. jejuni strains (BD-07 and BD-39). Mass spectrometry analysis confirmed the presence of GM1 and GD1a carbohydrate mimics in the LOS from C. jejuni BD-07 and BD-39. Both BD-10 and BD-67 express the same LOS outer core, which appears to be a novel structure displaying GA2 and GD3 mimicry. Up to 90-100% of serum reactivity to gangliosides in two patients (DK-07 and DK-39) was inhibited by 50 µg/ml of LOS from the autologous C. jejuni isolates. However, patient DK-07 developed an anti-GD1a immune response while patient DK-39 developed an anti-GM1 immune response.&lt;br/&gt; CONCLUSION:&lt;br/&gt; Carbohydrate mimicry between C. jejuni LOS and gangliosides, and cross-reactive serum antibody precipitate the majority of GBS cases in Bangladesh

On the universal outcome of star-formation: Is there a link between stars and brown-dwarfs?

(abridged) The recent evidence obtained by Briceno et al. that star-formation in Taurus-Auriga (TA) may be producing significantly fewer brown dwarfs (BDs) per star than the ONC is investigated by setting up a realistic model stellar plus BD population and explicitly taking into account a high binary proportion and dynamical evolution in the TA groups and the ONC. The Briceno result is reproduced almost exactly despite an identical IMF in both systems because many BD-BD and star-BD binaries are disrupted in the ONC thus freeing BDs, while the TA groups remain unevolved dynamically. However, the resulting populations do not have the correct star-star, star-BD and expecially BD-BD binary properties, even if a variable BD IMF is allowed for. The conclusion is therefore that BDs need to be added as a separate population which has its own binary properties. Such an extra population can have various origins which are briefly discussed in this contribution but more fully in an associated paper.Comment: MNRAS, accepted, 23 pages, 14 figures, LaTeX, two references adde

Impaired regulation of emotion: Neural correlates of reappraisal and distraction in bipolar disorder and unaffected relatives

Deficient emotion regulation has been proposed as a crucial pathological mechanism in bipolar disorder (BD). We therefore investigated emotion regulation impairments in BD, the related neural underpinnings and their etiological relevance for the disorder. Twenty-two euthymic patients with bipolar-I disorder and 17 unaffected first-degree relatives of BD-I patients, as well as two groups of healthy gender-, age- and education-matched controls (N=22/17, respectively) were included. Participants underwent functional magnetic resonance imaging while applying two different emotion regulation techniques, reappraisal and distraction, when presented with emotional images. BD patients and relatives showed impaired downregulation of amygdala activity during reappraisal, but not during distraction, when compared with controls. This deficit was correlated with the habitual use of reappraisal. The negative connectivity of amygdala and orbitofrontal cortex (OFC) observed during reappraisal in controls was reversed in BD patients and relatives. There were no significant differences between BD patients and relatives. As being observed in BD patients and unaffected relatives, deficits in emotion regulation through reappraisal may represent heritable neurobiological abnormalities underlying BD. The neural mechanisms include impaired control of amygdala reactivity to emotional stimuli and dysfunctional connectivity of the amygdala to regulatory control regions in the OFC. These are, thus, important aspects of the neurobiological basis of increased vulnerability for BD