Comorbidity Between Major Depression and Alcohol Use Disorder From Adolescence to Adulthood

Background—Limited information exists regarding the long-term development of comorbidity between Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD; abuse/dependence). Using a representative prospective study, we examine multiple aspects pertaining to MDD+AUD comorbidity, with a focus on the relation between disorders across periods (adolescence, early adulthood, adulthood) and cumulative impairments by age 30. Method—816 participants were diagnostically interviewed at ages 16, 17, 24, and 30. Results—Rates of comorbid MDD+AUD were low in adolescence (2%), but increased in early adulthood (10%) and adulthood (7%). Rates of cumulative comorbidity were elevated (21%). Most individuals with a history of MDD or AUD had the other disorder, except for women with MDD. Prospectively, adolescent AUD predicted early adult MDD, while early adult MDD predicted adult AUD. Compared to pure disorders, MDD+AUD was associated with higher risk of alcohol dependence, suicide attempt, lower global functioning, and life dissatisfaction. Conclusions—Lifetime rates of comorbid MDD+AUD were considerably higher than in crosssectional studies. Comorbidity was partly explained by bidirectional and developmentally-specific associations and predicted selected rather than generalized impairments. Clinically, our findings emphasize the need to always carefully assess comorbidity in patients with MDD or AUD, taking into account concurrency and developmental timing

Adolescent suicide attempts and adult adjustment

Background: Adolescent suicide attempts are disproportionally prevalent and frequently of low severity, raising questions regarding their long-term prognostic implications. In this study, we examined whether adolescent attempts were asso- ciated with impairments related to suicidality, psychopathology, and psychosocial functioning in adulthood (objective 1) and whether these impairments were better accounted for by concurrent adolescent confounders (objective 2). Method: Eight hundred and sixteen adolescents were assessed using interviews and question- naires at four time points from adolescence to adulthood. We examined whether lifetime suicide attempts in adolescence (by T2, mean age 17) predicted adult out- comes (by T4, mean age 30) using linear and logistic regressions in unadjusted models (objective 1) and adjusting for sociodemographic background, adolescent psychopathology, and family risk factors (objective 2). Results: In unadjusted analyses, adolescent suicide attempts predicted poorer adjustment on all outcomes, except those related to social role status. After adjustment, adolescent attempts remained predictive of axis I and II psychopathology (anxiety disorder, antisocial and borderline personality disorder symptoms), global and social adjustment, risky sex, and psychiatric treatment utilization. However, adolescent attempts no longer predicted most adult outcomes, notably suicide attempts and major depressive disorder. Secondary analyses indicated that associations did not differ by sex and attempt characteristics (intent, lethality, recurrence). Conclusions: Adolescent suicide attempters are at high risk of protracted and wide-ranging im- pairments, regardless of the characteristics of their attempt. Although attempts specifically predict (and possibly influence) several outcomes, results suggest that most impairments reflect the confounding contributions of other individual and family problems or vulnerabilites in adolescent attempters

Negative Life Events and Substance Use Moderate Cognitive Behavioral Adolescent Depression Prevention Intervention

Abstract. Investigate factors that amplify or mitigate the effects of an indicated cognitive behavioral (CB) depression prevention program for adolescents with elevated depressive symptoms. Using data from a randomized trial (Registration No. NCT00183417; n ¼ 173) in which adolescents (M age ¼ 15.5, SD ¼ 1.2) were assigned to a brief cognitive behavioral prevention program or an educational brochure control condition, we tested whether elevated motivation to reduce depression and initial depressive symptom severity amplified intervention effects and whether negative life events, social support deficits, and substance use attenuated intervention effects. Hierarchical linear modeling (HLM) indicated differential intervention effects for two of the five examined variables: negative life events and substance use. For adolescents at low and medium levels of substance use or negative life events, the CB intervention produced declines in depressive symptoms relative to controls. However, at high levels of substance use or negative life events, the CB intervention did not significantly reduce depressive symptoms in comparison to controls. Results imply that high-risk adolescents with either high rates of major life stress or initial substance use may require specialized depression prevention efforts

Quantum state engineering on an optical transition and decoherence in a Paul trap

A single Ca+ ion in a Paul trap has been cooled to the ground state of vibration with up to 99.9% probability. Starting from this Fock state |n=0> we have demonstrated coherent quantum state manipulation on an optical transition. Up to 30 Rabi oscillations within 1.4 ms have been observed. We find a similar number of Rabi oscillations after preparation of the ion in the |n=1> Fock state. The coherence of optical state manipulation is only limited by laser and ambient magnetic field fluctuations. Motional heating has been measured to be as low as one vibrational quantum in 190 ms.Comment: 4 pages, 5 figure

Cigarette smoke extract induced exosome release is mediated by depletion of exofacial thiols and can be inhibited by thiol-antioxidants

Introduction: Airway epithelial cells have been described to release extracellular vesicles (EVs) with pathological properties when exposed to cigarette smoke extract (CSE). As CSE causes oxidative stress, we investigated whether its oxidative components are responsible for inducing EV release and whether this could be prevented using the thiol antioxidants N-acetyl-L-cysteine (NAC) or glutathione (GSH). Methods: BEAS-2B cells were exposed for 24 h to CSE, H2O2, acrolein, 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), bacitracin, rutin or the anti-protein disulfide isomerase (PDI) antibody clone RL90; with or without NAC or GSH. EVs in media were measured using CD63(+)CD81(+) bead-coupled flow cytometry or tunable resistive pulse sensing (TRPS). For characterization by Western Blotting, cryo-transmission electron microscopy and TRPS, EVs were isolated using ultracentrifugation. Glutathione disulfide and GSH in cells were assessed by a GSH reductase cycling assay, and exofacial thiols using Flow cytometry. Results: CSE augmented the release of the EV subtype exosomes, which could be prevented by scavenging thiol-reactive components using NAC or GSH. Among thiol-reactive CSE components, H2O2 had no effect on exosome release, whereas acrolein imitated the NAC-reversible exosome induction. The exosome induction by CSE and acrolein was paralleled by depletion of cell surface thiols. Membrane impermeable thiol blocking agents, but not specific inhibitors of the exofacially located thiol-dependent enzyme PDI, stimulated exosome release. Summary/conclusion: Thiol-reactive compounds like acrolein account for CSE-induced exosome release by reacting with cell surface thiols. As acrolein is produced endogenously during inflammation, it may influence exosome release not only in smokers, but also in ex-smokers with chronic obstructive pulmonary disease. NAC and GSH prevent acrolein-and CSE-induced exosome release, which may contribute to the clinical benefits of NAC treatment

The role of MscL amphipathic N terminus indicates a blueprint for bilayer-mediated gating of mechanosensitive channels

The bacterial mechanosensitive channel MscL gates in response to membrane tension as a result of mechanical force transmitted directly to the channel from the lipid bilayer. MscL represents an excellent model system to study the basic biophysical principles of mechanosensory transduction. However, understanding of the essential structural components that transduce bilayer tension into channel gating remains incomplete. Here using multiple experimental and computational approaches, we demonstrate that the amphipathic N-terminal helix of MscL acts as a crucial structural element during tension-induced gating, both stabilizing the closed state and coupling the channel to the membrane. We propose that this may also represent a common principle in the gating cycle of unrelated mechanosensitive ion channels, allowing the coupling of channel conformation to membrane dynamics

Fusion algebra of critical percolation

We present an explicit conjecture for the chiral fusion algebra of critical percolation considering Virasoro representations with no enlarged or extended symmetry algebra. The representations we take to generate fusion are countably infinite in number. The ensuing fusion rules are quasi-rational in the sense that the fusion of a finite number of these representations decomposes into a finite direct sum of these representations. The fusion rules are commutative, associative and exhibit an sl(2) structure. They involve representations which we call Kac representations of which some are reducible yet indecomposable representations of rank 1. In particular, the identity of the fusion algebra is a reducible yet indecomposable Kac representation of rank 1. We make detailed comparisons of our fusion rules with the recent results of Eberle-Flohr and Read-Saleur. Notably, in agreement with Eberle-Flohr, we find the appearance of indecomposable representations of rank 3. Our fusion rules are supported by extensive numerical studies of an integrable lattice model of critical percolation. Details of our lattice findings and numerical results will be presented elsewhere.Comment: 12 pages, v2: comments and references adde