The externalizing and internalizing pathways to marijuana use initiation: Examining the synergistic effects of impulsiveness and sensation seeking.

Adolescent marijuana use has become increasingly more problematic compared with the past; thus, understanding developmental processes that increase the liability of marijuana use is essential. Two developmental pathways to adolescent substance use have been proposed: an externalizing pathway that emphasizes the expression of aggressive and delinquent behavior, and an internalizing pathway that emphasizes the role of depressive symptoms and negative affect. In this study, we aimed to examine the synergistic role of impulsiveness and sensation seeking in the two risk pathways to determine whether both high and low levels of the traits are risk factors for marijuana use. Our study included 343 adolescents (52% were girls, 78% identified as Hispanic) that oversampled high-risk youth (78% had a family history of substance use disorder), assessed biannually between the ages of 13-16 years old. Moderated mediation analyses revealed that high levels of sensation seeking indirectly predicted marijuana use through higher mean levels of externalizing behavior. The positive relationship between sensation seeking and externalizing behavior was only significant at high levels of impulsiveness. Conversely, low levels of sensation seeking indirectly predicted marijuana use through higher mean levels of internalizing behavior. The negative relationship between sensation seeking and internalizing behavior was only significant at low levels of impulsiveness. Collectively, these results demonstrate that high and low levels of both impulsiveness and sensation seeking confer increased risk of marijuana use, albeit through different mechanisms. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The Development of Externalizing and Internalizing Behaviors Among Youth With or Without a Family History of Substance Use Disorder: The Indirect Effects of Early-Life Stress and Impulsivity.

Youth with a family history of substance use disorder (FH+) are more prone to have externalizing and internalizing problems compared to youth without a family history of substance use disorder (FH-), increasing the likelihood of later maladjustment. However, mechanisms for this association remain understudied. In this longitudinal study, we examined if FH+ youth are more likely to experience early-life stressors (ELS), which in turn would increase impulsivity and the expression of externalizing and internalizing behaviors. Data were collected from youth and a parent (n = 386) during a baseline assessment (age 10-12 years) and every six months when the youth was 13-16 years old. In support of the primary hypothesis, FH+ youth reported higher levels of externalizing and internalizing behaviors through ELS to impulsivity providing a developmental pathway through which FH+ youth are more prone to externalizing and internalizing problems.

Deep brain stimulation of the internal capsule enhances human cognitive control and prefrontal cortex function.

Deep brain stimulation (DBS) is a circuit-oriented treatment for mental disorders. Unfortunately, even well-conducted psychiatric DBS clinical trials have yielded inconsistent symptom relief, in part because DBS' mechanism(s) of action are unclear. One clue to those mechanisms may lie in the efficacy of ventral internal capsule/ventral striatum (VCVS) DBS in both major depression (MDD) and obsessive-compulsive disorder (OCD). MDD and OCD both involve deficits in cognitive control. Cognitive control depends on prefrontal cortex (PFC) regions that project into the VCVS. Here, we show that VCVS DBS' effect is explained in part by enhancement of PFC-driven cognitive control. DBS improves human subjects' performance on a cognitive control task and increases theta (5-8Hz) oscillations in both medial and lateral PFC. The theta increase predicts subjects' clinical outcomes. Our results suggest a possible mechanistic approach to DBS therapy, based on tuning stimulation to optimize these neurophysiologic phenomena.

C60 chain phases on ZnPc/Ag(111) surfaces: Supramolecular organization driven by competing interactions.

Serpentine chain C60 phases were observed in scanning tunneling microscopy (STM) images of C60 layers on zinc phthalocyanine (ZnPc) or pentacene covered Ag(111) and Au(111) surfaces. This low-density, quasi-one-dimensional organization contrasts starkly with the close-packed hexagonal phases observed for C60 layers on bare metal substrates. STM was employed to perform a detailed investigation of these chain structures for C60/ZnPc/Ag(111) heterolayers. Motivated by the similarity of these chain phases, and the chain and stripe organization occurring in dipole-fluid systems, we investigated a model based on competing van der Waals attractions and electrostatic repulsions between C60 molecules as an explanation for the driving force behind these monolayer phases. Density functional theory (DFT) calculations revealed significant charge transfer to C60 from the Ag(111) substrate, through the intervening ZnPc layer, inducing electrostatic interactions between C60 molecules. Molecular dynamics simulations performed with attractive van der Waals interactions plus repulsive dipole-dipole interactions reproduced the C60 chain phases with dipole magnitudes consistent with DFT calculations.

Dissociable cortico-striatal connectivity abnormalities in major depression in response to monetary gains and penalties.

BACKGROUND: Individuals with major depressive disorder (MDD) are characterized by maladaptive responses to both positive and negative outcomes, which have been linked to localized abnormal activations in cortical and striatal brain regions. However, the exact neural circuitry implicated in such abnormalities remains largely unexplored. METHOD: In this study 26 unmedicated adults with MDD and 29 matched healthy controls (HCs) completed a monetary incentive delay task during functional magnetic resonance imaging (fMRI). Psychophysiological interaction (PPI) analyses probed group differences in connectivity separately in response to positive and negative outcomes (i.e. monetary gains and penalties). RESULTS: Relative to HCs, MDD subjects displayed decreased connectivity between the caudate and dorsal anterior cingulate cortex (dACC) in response to monetary gains, yet increased connectivity between the caudate and a different, more rostral, dACC subregion in response to monetary penalties. Moreover, exploratory analyses of 14 MDD patients who completed a 12-week, double-blind, placebo-controlled clinical trial after the baseline fMRI scans indicated that a more normative pattern of cortico-striatal connectivity pre-treatment was associated with greater improvement in symptoms 12 weeks later. CONCLUSIONS: These results identify the caudate as a region with dissociable incentive-dependent dACC connectivity abnormalities in MDD, and provide initial evidence that cortico-striatal circuitry may play a role in MDD treatment response. Given the role of cortico-striatal circuitry in encoding action-outcome contingencies, such dysregulated connectivity may relate to the prominent disruptions in goal-directed behavior that characterize MDD.

Pilot randomized trial demonstrating reversal of obesity-related abnormalities in reward system responsivity to food cues with a behavioral intervention.

OBJECTIVES: Obesity is associated with hyperactivation of the reward system for high-calorie (HC) versus low-calorie (LC) food cues, which encourages unhealthy food selection and overeating. However, the extent to which this hyperactivation can be reversed is uncertain, and to date there has been no demonstration of changes by behavioral intervention. SUBJECTS AND METHODS: We used functional magnetic resonance imaging to measure changes in activation of the striatum for food images at baseline and 6 months in a pilot study of 13 overweight or obese adults randomized to a control group or a novel weight-loss intervention. RESULTS: Compared to controls, intervention participants achieved significant weight loss (-6.3±1.0 kg versus +2.1±1.1 kg, P<0.001) and had increased activation for LC food images with a composition consistent with that recommended in the behavioral intervention at 6 months versus baseline in the right ventral putamen (P=0.04), decreased activation for HC images of typically consumed foods in the left dorsal putamen (P=0.01). There was also a large significant shift in relative activation favoring LC versus HC foods in both regions (P<0.04). CONCLUSIONS: This study provides the first demonstration of a positive shift in activation of the reward system toward healthy versus unhealthy food cues in a behavioral intervention, suggesting new avenues to enhance behavioral treatments of obesity.

Age at onset, course of illness and response to psychotherapy in bipolar disorder: results from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

BACKGROUND: The course of bipolar disorder progressively worsens in some patients. Although responses to pharmacotherapy appear to diminish with greater chronicity, less is known about whether patients' prior courses of illness are related to responses to psychotherapy. METHOD: Embedded in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was a randomized controlled trial of psychotherapy for bipolar depression comparing the efficacy of intensive psychotherapy with collaborative care (a three-session psycho-educational intervention). We assessed whether the number of previous mood episodes, age of illness onset, and illness duration predicted or moderated the likelihood of recovery and time until recovery from a depressive episode in patients in the two treatments. RESULTS: Independently of treatment condition, participants with one to nine prior depressive episodes were more likely to recover and had faster time to recovery than those with 20 or more prior depressive episodes. Participants with fewer than 20 prior manic episodes had faster time to recovery than those with 20 or more episodes. Longer illness duration predicted a longer time to recovery. Participants were more likely to recover in intensive psychotherapy than collaborative care if they had 10-20 prior episodes of depression [number needed to treat (NNT) = 2.0], but equally likely to respond to psychotherapy and collaborative care if they had one to nine (NNT = 32.0) or >20 (NNT = 9.0) depressive episodes. CONCLUSIONS: Number of previous mood episodes and illness duration are associated with the likelihood and speed of recovery among bipolar patients receiving psychosocial treatments for depression.

Decreased regional cerebral blood flow in medial prefrontal cortex during trauma-unrelated stressful imagery in Vietnam veterans with post-traumatic stress disorder.

BACKGROUND: Neuroimaging research has demonstrated medial prefrontal cortex (mPFC) hyporesponsivity and amygdala hyperresponsivity to trauma-related or emotional stimuli in post-traumatic stress disorder (PTSD). Relatively few studies have examined brain responses to the recollection of stressful, but trauma-unrelated, personal events in PTSD. In the current study, we sought to determine whether regional cerebral blood flow (rCBF) abnormalities in mPFC and amygdala in PTSD could be observed during the recollection of trauma-unrelated stressful personal events. METHOD: Participants were 35 right-handed male combat veterans (MCVs) and female nurse veterans (FNVs) who served in Vietnam: 17 (seven male, 10 female) with current military-related PTSD and 18 (nine male, nine female) with no current or lifetime PTSD. We used positron emission tomography (PET) and script-driven imagery to study rCBF during the recollection of trauma-unrelated stressful versus neutral and traumatic events. RESULTS: Voxelwise tests revealed significant between-group differences for the trauma-unrelated stressful versus neutral comparison in mPFC, specifically in the anterior cingulate cortex (ACC). Functional region of interest (ROI) analyses demonstrated that this interaction in mPFC represented greater rCBF decreases in the PTSD group during trauma-unrelated stressful imagery relative to neutral imagery compared to the non-PTSD group. No differential amygdala activation was observed between groups or in either group separately. CONCLUSIONS: Veterans with PTSD, compared to those without PTSD, exhibited decreased rCBF in mPFC during mental imagery of trauma-unrelated stressful personal experiences. Functional neuroanatomical models of PTSD must account for diminished mPFC responses that extend to emotional stimuli, including stressful personal experiences that are not directly related to PTSD.

BU and CY as conditioning regimen for autologous transplant in patients with multiple myeloma.

High-dose melphalan is considered the current standard of care among the preparative regimens used in peripheral blood autologous SCT (ASCT) for multiple myeloma (MM). We report the results of a single ASCT in 79 MM patients using the BU/CY conditioning regimen, with BU 1 mg/kg p.o. or 0.8 mg/kg i.v. every 6 h x 16 doses, and CY 60 mg/kg per day i.v. for 2 days. ASCT was carried out in first (62%) or subsequent remission/refractory disease (38%). For an overall RR of 86%, 48 and 20 patients achieved PR and CR, respectively. At a median follow-up of 41 months (range 2-132 months), the estimated median OS and PFS were 45 months (95% confidence interval (CI)=38-92) and 20 months (95% CI=15-25), respectively. The BU/CY regimen was well tolerated, and transplant-related mortality was 4%. Clinical outcomes of the BU/CY regimen are not superior to those obtained in historical controls with high-dose melphalan followed by a single ASCT. Therefore, considering even the greater complexity of administration of the BU/CY regimen compared with that of single-agent melphalan, we believe the latter should remain the conditioning regimen of choice for ASCT in MM.

Finding order in heterogeneity: types of quality-improvement intervention publications.

BACKGROUND: Stakeholders in quality improvement agree on the need for augmenting and synthesising the scientific literature supporting it. The diversity of perspectives, approaches, and contexts critical to advancing quality improvement science, however, creates challenges. The paper explores the heterogeneity in clinical quality improvement intervention (QII) publications. METHODS: A preliminary classification framework was developed for QII articles, aiming for categories homogeneous enough to support coherent scientific discussion on QII reporting standards and facilitate systematic review. QII experts were asked to identify articles important to QII science. The framework was tested and revised by applying it to the article set. The final framework screened articles into (1) empirical literature on development and testing of QIIs; (2) QII stories, theories, and frameworks; (3) QII literature syntheses and meta-analyses; or (4) development and testing of QII-related tools. To achieve homogeneity, category (1) required division into (1a) development of QIIs; 1(b) history, documentation, or description of QIIs; or (1c) success, effectiveness or impact of QIIs. RESULTS: By discussing unique issues and established standards relevant to each category, QII stakeholders can advance QII practice and science, including the scope and conduct of systematic literature reviews.

Spatial first-passage statistics of Al/Si(111)-(square root 3 x square root 3) step fluctuations.

Spatial step edge fluctuations on a multicomponent surface of Al/Si(111)-(square root 3 x square root 3) were measured via scanning tunneling microscopy over a temperature range of 720-1070 K, for step lengths of L=65-160 nm. Even though the time scale of fluctuations of steps on this surface varies by orders of magnitude over the indicated temperature range, measured first-passage spatial persistence and survival probabilities are temperature independent. The power law functional form for spatial persistence probabilities is confirmed and the symmetric spatial persistence exponent is measured to be theta=0.498+/-0.062 in agreement with the theoretical prediction theta=1/2. The survival probability is found to scale directly with y/L, where y is the distance along the step edge. The form of the survival probabilities agrees quantitatively with the theoretical prediction, which yields exponential decay in the limit of small y/L. The decay constant is found experimentally to be y(s)/L=0.076+/-0.033 for y/L

Role of conformation in the electronic properties of chemisorbed pyridine on Cu(110): an STM/STS study.

Pyridine was chemisorbed on Cu(110) at 10 K and observed using STM at 5 K as dosed and after annealing to temperatures between 20 and 300 K. At very low coverage, two molecular species with different apparent heights are observed to coexist. The higher species is assigned to a pyridine molecule bonded with its symmetry axis perpendicular to the surface plane, while the lower species is assigned to a pyridine molecule that is tilted down toward the surface plane. At low coverage, the tilted pyridine species predominates on the surface, but as the total surface coverage of pyridine increases, the molecules stand up until the upright geometry becomes favored. Measurements of the STS of the two species show different molecular resonances derived from the lowest unoccupied pyridine pi* orbitals. The tilted pyridine species has a peak in the unoccupied local density of states at 2.6 +/- 0.1 eV, whereas the upright pyridine species has a peak at 2.3 +/- 0.1 eV.

Local spectroscopy of image-potential-derived states: from single molecules to monolayers of benzene on Cu(111).

Stark-shifted image-potential states were measured with an STM tip for benzene adsorbed on a Cu(111) surface. A single benzene molecule locally shifts the position of the first image state toward the Fermi level by 0.2 eV relative to its position on the clean surface. The energetic position of this molecule-modified state shifts to lower energy with increasing coverage of benzene on the surface. This is attributed to local surface potential changes that are correlated with the lowering of the crystal work function due to adsorption of benzene.

Spiral evolution in a confined geometry.

Supported nanoscale lead crystallites with a step emerging from a noncentered screw dislocation on the circular top facet were prepared by rapid cooling from just above the melting temperature. STM observations of the top facet show a nonuniform rotation rate and shape of the spiral step as the crystallite relaxes. These features can be accurately modeled using curvature driven dynamics, as in classical models of spiral growth, with boundary conditions fixing the dislocation core and regions of the step lying along the outer facet edge.

Sampling-time effects for persistence and survival in step structural fluctuations.

The effects of sampling rate and total measurement time have been determined for single-point measurements of step fluctuations within the context of first-passage properties. Time dependent scanning tunneling microscopy has been used to evaluate step fluctuations on Ag(111) films grown on mica as a function of temperature (300-410 K) , on screw dislocations on the facets of Pb crystallites at 320 K , and on Al-terminated Si(111) over the temperature range 770-970 K . Although the fundamental time constant for step fluctuations on Ag and Al/Si varies by orders of magnitude over the temperature ranges of measurement, no dependence of the persistence amplitude on temperature is observed. Instead, the persistence probability is found to scale directly with t/delta t where delta t is the time interval used for sampling. Survival probabilities show a more complex scaling dependence, which includes both the sampling interval and the total measurement time t(m) . Scaling with t/delta t occurs only when delta t/ t(m) is a constant. We show that this observation is equivalent to theoretical predictions that the survival probability will scale as delta t/ L(z) , where L is the effective length of a step. This implies that the survival probability for large systems, when measured with fixed values of t(m) or delta t , should also show little or no temperature dependence.

Infinite family of persistence exponents for interface fluctuations.

We show experimentally and theoretically that the persistence of large deviations in equilibrium step fluctuations is characterized by an infinite family of independent exponents. These exponents are obtained by carefully analyzing dynamical experimental images of Al/Si(111) and Ag(111) equilibrium steps fluctuating at high (970 K) and low (320 K) temperatures, respectively, and by quantitatively interpreting our observations on the basis of the corresponding coarse-grained discrete and continuum theoretical models for thermal surface step fluctuations under attachment/detachment ("high-temperature") and edge-diffusion limited kinetics ("low-temperature"), respectively.

Eight-year follow-up study of brain atrophy in patients with MS.

OBJECTIVE: To characterize whole-brain atrophy in relapsing-remitting MS (RRMS) patients over an 8-year period. The specific goals of this study were to determine if brain atrophy is related to subsequent disability status and to identify MRI correlates of atrophy progression. METHODS: A follow-up study was conducted to reassess patients from a phase III trial of interferon beta-1a (IFNbeta-1a) 8 years after randomization. Clinical and MRI data from 172 patients followed over 2 years in the original trial were used as baseline data. Follow-up data were obtained on 160 patients, including 134 patients with follow-up MRI examinations. Brain atrophy was estimated by automated calculation of brain parenchymal fraction. The relation between atrophy during the original trial and disability status at follow-up was determined. Correlations were also determined between lesion measurements from the original trial and the brain parenchymal fraction at follow-up. RESULTS: Brain atrophy was correlated with subsequent disability status. Atrophy rate during the original trial was the most significant MRI predictor of disability status at follow-up. Brain atrophy at follow-up was related to lesion volumes measured during the original trial. CONCLUSIONS: The relation between atrophy progression and subsequent neurologic disability status suggests that atrophy progression during RRMS is clinically relevant. Therefore, atrophy progression may be a useful marker for disease progression in clinical trials. The relation between lesions and subsequent atrophy indicates that brain atrophy may be related to focal tissue damage at earlier points in time, but important predisposing or other factors contributing to atrophy remain undefined.

Experimental persistence probability for fluctuating steps.

The persistence behavior for fluctuating steps on the Si(111)-(sqrt[3]xsqrt[3])R30 degrees -Al surface was determined by analyzing time-dependent STM images for temperatures between 770 and 970 K. Using the standard persistence definition, the measured persistence probability displays power-law decay with an exponent of theta=0.77+/-0.03. This is consistent with the value of theta=3/4 predicted for attachment-detachment limited step kinetics. If the persistence analysis is carried out in terms of return to a fixed-reference position, the measured probability decays exponentially. Numerical studies of the Langevin equation used to model step motion corroborate the experimental observations.