Item response modeling of DSM-IV mania symptoms in two representative US epidemiological samples

BACKGROUND: There is considerable debate surrounding the effective measurement of DSM-IV symptoms used to assess manic disorders in epidemiological samples. METHODS: Using two nationally representative datasets, the National Epidemiological Survey of Alcohol and Related Conditions (NESARC, N=43,093 at Wave 1, N=34,653 at 3-year follow-up) and the National Comorbidity Survey-Replication (NCS-R, N=9,282), we examined the psychometric properties of symptoms used to assess DSM-IV mania. The predictive utility of the mania factor score was tested using the 3-year follow-up data in NESARC. RESULTS: Criterion B symptoms were unidimensional (single factor) in both samples. The symptoms assessing flight of ideas, distractibility and increased goal-directed activities had high factor loadings (0.70–0.93) with moderate rates of endorsement thus providing good discrimination between individuals with and without mania. The symptom assessing grandiosity performed less well in both samples. The quantitative mania factor score was a good predictor of more severe disorders at 3-year follow-up in the NESARC sample, even after controlling for a past history of DSM-IV diagnosis of manic disorder. CONCLUSION: These analyses suggest that questions based on some DSM symptoms effectively discriminate between individuals at high and low liability to mania, while others do not. A quantitative mania factor score may aid in predicting recurrence for patients with a history of mania. Methods for assessing mania using structured interviews in the absence of clinical assessment require further refinement

A Keck High Resolution Spectroscopic Study of the Orion Nebula Proplyds

We present the results of spectroscopy of four bright proplyds in the Orion Nebula obtained at a velocity resolution of 6 km/s. After careful isolation of the proplyd spectra from the confusing nebular radiation, the emission line profiles are compared with those predicted by realistic dynamic/photoionization models of the objects. The spectral line widths show a clear correlation with ionization potential, which is consistent with the free expansion of a transonic, ionization-stratified, photoevaporating flow. Fitting models of such a flow simultaneously to our spectra and HST emission line imaging provides direct measurements of the proplyd size, ionized density and outflow velocity. These measurements confirm that the ionization front in the proplyds is approximately D-critical and provide the most accurate and robust estimate to date of the proplyd mass loss rate. Values of 0.7E-6 to 1.5E-6 Msun/year are found for our spectroscopic sample, although extrapolating our results to a larger sample of proplyds implies that 0.4E-6 Msun/year is more typical of the proplyds as a whole. In view of the reported limits on the masses of the circumstellar disks within the proplyds, the length of time that they can have been exposed to ionizing radiation should not greatly exceed 10,000 years - a factor of 30 less than the mean age of the proplyd stars. We review the various mechanisms that have been proposed to explain this situation, and conclude that none can plausibly work unless the disk masses are revised upwards by a substantial amount.Comment: 23 pages, 8 figures, uses emulateapj.sty, accepted for publication in The Astronomical Journal (scheduled November 1999

Predictors of subgroups based on maximum drinks per occasion over six years for 833 adolescents and young adults in COGA.

ObjectiveA person's pattern of heavier drinking often changes over time, especially during the early drinking years, and reflects complex relationships among a wide range of characteristics. Optimal understanding of the predictors of drinking during times of change might come from studies of trajectories of alcohol intake rather than cross-sectional evaluations.MethodThe patterns of maximum drinks per occasion were evaluated every 2 years between the average ages of 18 and 24 years for 833 subjects from the Collaborative Study on the Genetics of Alcoholism. Latent class growth analysis identified latent classes for the trajectories of maximum drinks, and then logistic regression analyses highlighted variables that best predicted class membership.ResultsFour latent classes were found, including Class 1 (69%), with about 5 maximum drinks per occasion across time; Class 2 (15%), with about 9 drinks at baseline that increased to 18 across time; Class 3 (10%), who began with a maximum of 18 drinks per occasion but decreased to 9 over time; and Class 4 (6%), with a maximum of about 22 drinks across time. The most consistent predictors of higher drinking classes were female sex, a low baseline level of response to alcohol, externalizing characteristics, prior alcohol and tobacco use, and heavier drinking peers.ConclusionsFour trajectory classes were observed and were best predicted by a combination of items that reflected demography, substance use, level of response and externalizing phenotypes, and baseline environment and attitudes

Constraints on the Circumstellar Disk Masses in the IC 348 Cluster

A 5.2' x 5.2' region toward the young cluster IC 348 has been imaged in the millimeter continuum at 4.0" x 4.9" resolution with the OVRO interferometer to a RMS noise level of 0.75 mJy/beam at 98 GHz. The data are used to constrain the circumstellar disk masses in a cluster environment at an age of about 2 Myr. The mosaic encompasses 95 known members of the IC 348 cluster with a stellar mass distribution that peaks at 0.2-0.5 Msun. None of the stars are detected in the millimeter continuum at an intensity level of 3 sigma or greater. The mean observed flux for the ensemble of 95 stars is 0.22 +/- 0.08 mJy. Assuming a dust temperature of 20 K, a mass opacity coefficient of kappa_o = 0.02 cm^2/g at 1300 um, and a power law index of beta=1 for the particle emissivity, these observations imply that the 3 sigma upper limit to the disk mass around any individual star is 0.025 Msun, and that the average disk mass is 0.002 +/- 0.001 Msun. The absence of disks with masses in excess of 0.025 Msun in IC 348 is different at the about 3 sigma confidence level from Taurus, where about 14% of the stars in an optically selected sample have such disk masses. Compared with the minimum mass needed to form the planets in our solar system (about 0.01 Msun), the lack of massive disks and the low mean disk mass in IC 348 suggest either that planets more massive than a few Jupiter masses will form infrequently around 0.2-0.5 Msun stars in IC 348, or that the process to form such planets has significantly depleted the disk of small dust grains on time scales less than the cluster age of about 2 Myr.Comment: accepted by A

Salivary melatonin onset in youth at familial risk for bipolar disorder

Melatonin secretion and polysomnography (PSG) were compared among a group of healthy adolescents who were at high familial risk for bipolar disorder (HR) and a second group at low familial risk (LR). Adolescent participants (n = 12) were a mean age 14 ± 2.3 years and included 8 females and 4 males. Saliva samples were collected under standardized condition light (red light) and following a 200 lux light exposure over two consecutive nights in a sleep laboratory. Red Light Melatonin onset (RLMO) was defined as saliva melatonin level exceeding the mean of the first 3 readings plus 2 standard deviations. Polysomnography was also completed during each night. HR youth, relative to LR, experienced a significantly earlier melatonin onset following 200 lux light exposure. Polysomnography revealed that LR youth, relative to HR, spent significantly more time in combined stages 3 and 4 (deep sleep) following red light exposure. Additionally, regardless of the group status (HR or LR), there was no significant difference in Red Light Melatonin Onset recorded at home or in the laboratory, implying its feasibility and reliability

Interferometric Observations of the T Tauri Stars in the MBM 12 Cloud

We have carried out a millimeter interferometric continuum survey toward 7 YSOs in the MBM 12 cloud. Thermal emissions associated with 2 YSOs were detected above the 3-$\sigma$ level at 2.1 mm, and one also showed a 1.3 mm thermal emission. Another object was marginally detected at 2.1 mm. Spectral energy distributions of the YSOs are well fitted by a simple power-law disk model. Masses of the circumstellar disks are estimated to be an order of 0.05 M_{\sun}. The circumstellar disks in the MBM 12 cloud have properties in common with the disks in nearby star-forming regions, in terms of disk parameters such as a disk mass, as well as an infrared excess.Comment: 9 pages, 3 figures, accepted by ApJ Letter

What Should a Psychiatrist Know About Genetics? Review and Recommendations From the Residency Education Committee of the International Society of Psychiatric Genetics.

The International Society of Psychiatric Genetics (ISPG) created a Residency Education Committee with the purpose of identifying key genetic knowledge that should be taught in psychiatric training programs. Thirteen committee members were appointed by the ISPG Board of Directors, based on varied training, expertise, gender, and national origin. The Committee has met quarterly for the past 2 years, with periodic reports to the Board and to the members of the Society. The information summarized includes the existing literature in the field of psychiatric genetics and the output of ongoing large genomics consortia. An outline of clinically relevant areas of genetic knowledge was developed, circulated, and approved. This document was expanded and annotated with appropriate references, and the manuscript was developed. Specific information regarding the contribution of common and rare genetic variants to major psychiatric disorders and treatment response is now available. Current challenges include the following: (1) Genetic testing is recommended in the evaluation of autism and intellectual disability, but its use is limited in current clinical practice. (2) Commercial pharmacogenomic testing is widely available, but its utility has not yet been clearly established. (3) Other methods, such as whole exome and whole genome sequencing, will soon be clinically applicable. The need for informed genetic counseling in psychiatry is greater than ever before, knowledge in the field is rapidly growing, and genetic education should become an integral part of psychiatric training

Defining alcohol-related phenotypes in humans. The Collaborative Study on the Genetics of Alcoholism.

Alcoholism is a disease that runs in families and results at least in part from genetic risk factors. The Collaborative Study on the Genetics of Alcoholism (COGA) is a Federally funded effort to identify and characterize those genetic factors. The study involves more than 1,000 alcoholic subjects and their families, with researchers conducting comprehensive psychological, physiological, electrophysiological, and genetic analyses of the participants. These analyses have identified several traits, or phenotypes, that appear to be genetically determined, such as the presence of alcohol dependence, the level of response to alcohol, the presence of coexisting depression, or the maximum number of drinks a person consumes per occasion. Genetic analyses have identified regions on several chromosomes that are associated with these phenotypes and need to be studied further

Molecular basis for functional diversity among microbial Nep1-like proteins

Necrosis and ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs) are secreted by several phytopathogenic microorganisms. They trigger necrosis in various eudicot plants upon binding to plant sphingolipid glycosylinositol phosphorylceramides (GIPC). Interestingly, HaNLP3 from the obligate biotroph oomycete Hyaloperonospora arabidopsidis does not induce necrosis. We determined the crystal structure of HaNLP3 and showed that it adopts the NLP fold. However, the conformations of the loops surrounding the GIPC headgroup-binding cavity differ from those of cytotoxic Pythium aphanidermatum NLPPya. Essential dynamics extracted from \u3bcs-long molecular dynamics (MD) simulations reveals a limited conformational plasticity of the GIPC-binding cavity in HaNLP3 relative to toxic NLPs. This likely precludes HaNLP3 binding to GIPCs, which is the underlying reason for the lack of toxicity. This study reveals that mutations at key protein regions cause a switch between nontoxic and toxic phenotypes within the same protein scaffold. Altogether, these data provide evidence that protein flexibility is a distinguishing trait of toxic NLPs and highlight structural determinants for a potential functional diversification of non-toxic NLPs utilized by biotrophic plant pathogens

Genetic and environment effects on structural neuroimaging endophenotype for bipolar disorder: a novel molecular approach

We investigated gene–environment effects on structural brain endophenotype in bipolar disorder (BD) using a novel method of combining polygenic risk scores with epigenetic signatures since traditional methods of examining the family history and trauma effects have significant limitations. The study enrolled 119 subjects, including 55 BD spectrum (BDS) subjects diagnosed with BD or major depressive disorder (MDD) with subthreshold BD symptoms and 64 non-BDS subjects comprising 32 MDD subjects without BD symptoms and 32 healthy subjects. The blood samples underwent genome-wide genotyping and methylation quantification. We derived polygenic risk score (PRS) and methylation profile score (MPS) as weighted summations of risk single nucleotide polymorphisms and methylation probes, respectively, which were considered as molecular measures of genetic and environmental risks for BD. Linear regression was used to relate PRS, MPS, and their interaction to 44 brain structure measures quantified from magnetic resonance imaging (MRI) on 47 BDS subjects, and the results were compared with those based on family history and childhood trauma. After multiplicity corrections using false discovery rate (FDR), MPS was found to be negatively associated with the volume of the medial geniculate thalamus (FDR = 0.059, partial R2 = 0.208). Family history, trauma scale, and PRS were not associated with any brain measures. PRS and MPS show significant interactions on whole putamen (FDR = 0.09, partial R2 = 0.337). No significant gene–environment interactions were identified for the family history and trauma scale. PRS and MPS generally explained greater proportions of variances of the brain measures (range of partial R2 = [0.008, 0.337]) than the clinical risk factors (range = [0.004, 0.228])