Familial aggregation of migraine and depression: Insights from a large Australian twin sample

Free to read\ud \ud Objectives: This research examined the familial aggregation of migraine, depression, and their co-occurrence.\ud \ud Methods: Diagnoses of migraine and depression were determined in a sample of 5,319 Australian twins. Migraine was diagnosed by either self-report, the ID migraine™ Screener, or International Headache Society (IHS) criteria. Depression was defined by fulfilling either major depressive disorder (MDD) or minor depressive disorder (MiDD) based on the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. The relative risks (RR) for migraine and depression were estimated in co-twins of twin probands reporting migraine or depression to evaluate their familial aggregation and co-occurrence.\ud \ud Results: An increased RR of both migraine and depression in co-twins of probands with the same trait was observed, with significantly higher estimates within monozygotic (MZ) twin pairs compared to dizygotic (DZ) twin pairs. For cross-trait analysis, the RR for migraine in co-twins of probands reporting depression was 1.36 (95% CI: 1.24–1.48) in MZ pairs and 1.04 (95% CI: 0.95–1.14) in DZ pairs; and the RR for depression in co-twins of probands reporting migraine was 1.26 (95% CI: 1.14–1.38) in MZ pairs and 1.02 (95% CI: 0.94–1.11) in DZ pairs. The RR for strict IHS migraine in co-twins of probands reporting MDD was 2.23 (95% CI: 1.81–2.75) in MZ pairs and 1.55 (95% CI: 1.34–1.79) in DZ pairs; and the RR for MDD in co-twins of probands reporting IHS migraine was 1.35 (95% CI: 1.13–1.62) in MZ pairs and 1.06 (95% CI: 0.93–1.22) in DZ pairs.\ud \ud Conclusions: We observed significant evidence for a genetic contribution to familial aggregation of migraine and depression. Our findings suggest a bi-directional association between migraine and depression, with an increased risk for depression in relatives of probands reporting migraine, and vice versa. However, the observed risk for migraine in relatives of probands reporting depression was considerably higher than the reverse. These results add further support to previous studies suggesting that patients with comorbid migraine and depression are genetically more similar to patients with only depression than patients with only migraine

Shared genetic factors underlie migraine and depression

Free to read\ud \ud Migraine frequently co-occurs with depression. Using a large sample of Australian twin pairs, we aimed to characterize the extent to which shared genetic factors underlie these two disorders. Migraine was classified using three diagnostic measures, including self-reported migraine, the ID migraine screening tool, or migraine without aura (MO) and migraine with aura (MA) based on International Headache Society (IHS) diagnostic criteria. Major depressive disorder (MDD) and minor depressive disorder (MiDD) were classified using the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. Univariate and bivariate twin models, with and without sex-limitation, were constructed to estimate the univariate and bivariate variance components and genetic correlation for migraine and depression. The univariate heritability of broad migraine (self-reported, ID migraine, or IHS MO/MA) and broad depression (MiDD or MDD) was estimated at 56% (95% confidence interval [CI]: 53-60%) and 42% (95% CI: 37-46%), respectively. A significant additive genetic correlation (r G = 0.36, 95% CI: 0.29-0.43) and bivariate heritability (h 2 = 5.5%, 95% CI: 3.6-7.8%) was observed between broad migraine and depression using the bivariate Cholesky model. Notably, both the bivariate h 2 (13.3%, 95% CI: 7.0-24.5%) and r G (0.51, 95% CI: 0.37-0.69) estimates significantly increased when analyzing the more narrow clinically accepted diagnoses of IHS MO/MA and MDD. Our results indicate that for both broad and narrow definitions, the observed comorbidity between migraine and depression can be explained almost entirely by shared underlying genetically determined disease mechanisms

The Mass Function of Super Giant Molecular Complexes and Implications for Forming Young Massive Star Clusters in the Antennae (NGC 4038/39)

We have used previously published observations of the CO emission from the Antennae (NGC 4038/39) to study the detailed properties of the super giant molecular complexes with the goal of understanding the formation of young massive star clusters. Over a mass range from 5E6 to 9E8 solar masses, the molecular complexes follow a power-law mass function with a slope of -1.4 +/- 0.1, which is very similar to the slope seen at lower masses in molecular clouds and cloud cores in the Galaxy. Compared to the spiral galaxy M51, which has a similar surface density and total mass of molecular gas, the Antennae contain clouds that are an order of magnitude more massive. Many of the youngest star clusters lie in the gas-rich overlap region, where extinctions as high as Av~100 imply that the clusters must lie in front of the gas. Combining data on the young clusters, thermal and nonthermal radio sources, and the molecular gas suggests that young massive clusters could have formed at a constant rate in the Antennae over the last 160 Myr and that sufficient gas exists to sustain this cluster formation rate well into the future. However, this conclusion requires that a very high fraction of the massive clusters that form initially in the Antennae do not survive as long as 100 Myr. Finally, we compare our data with two models for massive star cluster formation and conclude that the model where young massive star clusters form from dense cores within the observed super giant molecular complexes is most consistent with our current understanding of this merging system. (abbreviated)Comment: 40 pages, four figures; accepted for publication in Ap

High-Resolution Imaging of Molecular Gas and Dust in the Antennae (NGC 4038/39): Super Giant Molecular Complexes

We present new aperture synthesis CO maps of the Antennae (NGC 4038/39) obtained with the Caltech Millimeter Array. These sensitive images show molecular emission associated with the two nuclei and a partial ring of star formation to the west of NGC 4038, as well as revealing the large extent of the extra-nuclear region of star formation (the ``overlap region''), which dominates the CO emission from this system. The largest molecular complexes have masses of 3-6x10^8 M_sun, typically an order of magnitude larger than the largest structures seen to date in more quiescent galaxy disks. The extremely red luminous star clusters identified previously with HST are well-correlated with the CO emission, which supports the conclusion that they are highly embedded young objects rather than old globular clusters. There is an excellent correlation between the CO emission and the 15 micron emission seen with ISO, particularly for the brightest regions. The most massive complexes in the overlap region have similar [NeIII]/[NeII] ratios, which implies that all these regions are forming many massive stars. However, only the brightest mid-infrared peak shows strong, rising continuum emission longward of 10 microns, indicative of very small dust grains heated to high temperatures by their proximity to nearby luminous stars. Since these grains are expected to be removed rapidly from the immediate environment of the massive stars, it is possible that this region contains very young (< 1 Myr) sites of star formation. Alternatively, fresh dust grains could be driven into the sphere of influence of the massive stars, perhaps by the bulk motions of two giant molecular complexes. The kinematics and morphology of the CO emission in this region provide some support for this second scenario.Comment: Accepted for publication in The Astrophysical Journal, 13 pages, 5 figures, higher quality color images available at http://www.astro.cornell.edu/staff/vassilis/papers/ngc4038_co.ps.g

A genome-wide association study of self-rated health

Self-rated health questions have been proven to be a highly reliable and valid measure of overall health as measured by other indicators in many population groups. It also has been shown to be a very good predictor of mortality, chronic or severe diseases, and the need for services, and is positively correlated with clinical assessments. Genetic factors have been estimated to account for 25-64% of the variance in the liability of self-rated health. The aim of the present study was to identify Single Nucleotide Polymorphisms (SNPs) underlying the heritability of self-rated health by conducting a genome-wide association analysis in a large sample of 6,706 Australian individuals aged 18-92. No genome wide significant SNPs associated with self-rated health could be identified, indicating that self-rated health may be influenced by a large number of SNPs with very small effect size. A very large sample will be needed to identify these SNPs

From alcohol initiation to tolerance to problems: Discordant twin modeling of a developmental process

AbstractThe current study examined a stage-based alcohol use trajectory model to test for potential causal effects of earlier drinking milestones on later drinking milestones in a combined sample of two cohorts of Australian monozygotic and same-sex dizygotic twins (N= 7,398, ageM= 30.46,SD= 2.61, 61% male, 56% monozygotic twins). Ages of drinking, drunkenness, regular drinking, tolerance, first nontolerance alcohol use disorder symptom, and alcohol use disorder symptom onsets were assessed retrospectively. Ages of milestone attainment (i.e., age-of-onset) and time between milestones (i.e., time-to-event) were examined via frailty models within a multilevel discordant twin design. For age-of-onset models, earlier ages of onset of antecedent drinking milestones increased hazards for earlier ages of onset for more proximal subsequent drinking milestones. For the time-to-event models, however, earlier ages of onset for the “starting” milestone decreased risk for a shorter time period between the starting and the “ending” milestone. Earlier age of onset of intermediate milestones between starting and ending drinking milestones had the opposite effect, increasing risk for a shorter time period between the starting and ending milestones. These results are consistent with a causal effect of an earlier age of drinking milestone onset on temporally proximal subsequent drinking milestones.</jats:p