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Objective: Cross-sectional and preliminary longitudinal findings suggest that cyclical ovarian hormone fluctuations influence acute suicide risk. The authors provide the first analyses in females with suicidality to investigate which daily symptoms covary with suicidal ideation and planning thoughts, the role of the menstrual cycle in daily symptom variation, how daily fluctuations in symptoms mediate the menstrual cycle-suicidality relationship, and how these associations vary across individuals., Methods: Naturally cycling psychiatric outpatients (N=119) with past-month suicidal ideation provided daily ratings of psychiatric symptoms (depression, hopelessness, anxiety, feeling overwhelmed, agitation, anhedonia, worthlessness, rejection sensitivity, anger, perceived burdensomeness, and interpersonal conflict), suicidal ideation, and suicidal planning across at least one menstrual cycle. Symptom ratings were decomposed into trait (person-centered mean) and state (daily person-centered mean deviation) components. Five cycle phases were identified in relation to menses onset and ovulation (surge in urine luteinizing hormone level). Hypotheses were tested in multilevel structural equation models., Results: Nearly all psychiatric symptoms covaried with fluctuations in daily suicidal ideation, and a limited set of symptoms (depression, hopelessness, rejection sensitivity, and perceived burdensomeness) predicted within-person increases in suicidal planning. Many patients demonstrated perimenstrual worsening of psychiatric symptoms, suicidal ideation, and suicidal planning. Depressive symptoms (depression, hopelessness, perceived burdensomeness, and anhedonia) were the most robust statistical mediators predicting perimenstrual exacerbation of suicidality., Conclusions: Research on the menstrual cycle and suicide has been limited historically by small, cross-sectional samples. This study provides the first evidence that measuring day-to-day correlates of suicidality in a large transdiagnostic sample of females with suicidal ideation can contribute to understanding the pathways by which the menstrual cycle influences acute suicide risk., Competing Interests: The authors report no financial relationships with commercial interests.

Rationale: Stimulant drugs like methamphetamine (MA) activate brain reward circuitry, which is linked to the development of problematic drug use. It is not clear how drugs like MA alter neural response to a non-drug reward., Objectives: We examined how acute MA impacts neural response to receipt of a monetary reward relative to a loss in healthy adults. We hypothesized that MA (vs. placebo) would increase mesolimbic neural activation to reward, relative to loss., Methods: In a within-subject, randomized, cross-over, double-blind, placebo-controlled design, 41 healthy adults completed the Doors monetary reward task during fMRI after ingestion of placebo or 20 mg MA. We examined drug effects on neural response to reward receipt (Win vs. Loss) using a priori anatomical striatal regions of interest (nucleus accumbens (NAcc), caudate, putamen)., Results: MA decreased NAcc BOLD activation to reward vs loss compared to placebo (p=.007) without altering caudate or putamen BOLD activation. Similar effects for reward vs. loss were obtained using whole brain analysis. Additional exploratory ROI analysis comparing reward and loss activation relative to a neutral "fixation" period indicated that MA increased NAcc BOLD activation during loss trials, without decreasing activation during win trials., Conclusions: This preliminary evidence suggests that MA increases NAcc neural response to the receipt of monetary loss. Additional studies are needed to replicate our findings and clarify the mechanisms contributing to altered mesolimbic neural response to reward and loss receipt during stimulant intoxication., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Disruptions in neural responses to reward are implicated in risk for Alcohol Use Disorder (AUD) and Major Depressive Disorder (MDD). It is not clear whether these findings extend to those in remission from AUD and MDD, a critical question as studies of remission can (a) rule out effects due to current symptoms, and (b) can reveal potential trait-like differences., Methods: Individuals with and without remitted AUD (rAUD) and/or rMDD (rMDD) were drawn from a larger study to create four groups: rAUD (n = 54), rMDD (n = 66), rAUD + rMDD (n = 53), and a community control group (CCG; n = 81). Participants completed a validated monetary reward task during electroencephalogram (EEG). Multilevel models examined group differences in event-related potentials and time-frequency indices of reward and loss responsiveness, namely, reward positivity (RewP), feedback negativity (FN), reward-related delta power, and loss-related theta power., Results: Analyses revealed that the rAUD + rMDD group had significantly higher reward-related delta activity than the three other groups (p-values < 0.01), which did not differ from each other. Sensitivity analyses revealed this relationship fell just above the threshold set for significance after controlling for residual current MDD and AUD symptoms (p =.05). There were no other group differences or significant interactions (p-values > 0.05)., Conclusions: To our knowledge, this is the first study to show that individuals with remitted AUD and MDD demonstrate increased sensitivity to rewards compared to individuals with remitted AUD alone, MDD alone, and without AUD or MDD. These findings suggest heightened motivational salience to reward might be an important factor in comorbid AUD and MDD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The cognitive control network (CCN) is an important network responsible for performing and modulating executive functions. In adolescents, alcohol use has been associated with weaker cognitive control, higher reward sensitivity, and later-in-life alcohol problems. Given that the CCN continues to develop into young adulthood, it is important to understand relations between early alcohol use, the CCN, and reward networks. Participants included individuals 18-23 years without alcohol use disorder. Based upon self-reported age of first alcoholic drink, participants were split into two groups: Early (onset) Drinkers (first drink < age 18, N = 52) and Late (onset) Drinkers (first drink > age 18, N = 44). All participants underwent an 8-minute resting-state fMRI scan. Seed regions of interest included the anterior dorsolateral prefrontal cortex (DLPFC), amygdala, and ventral striatum. Early Drinkers demonstrated significant reduced connectivity of CCN regions, including bilateral anterior DLPFC, compared to Late Drinkers. There were no significant differences between Early and Late Drinkers in connectivity between reward and CCN regions. These results suggest that individuals who begin drinking alcohol earlier in life may have alterations in the development of the CCN; however, longitudinal research is necessary to determine whether lower connectivity precedes or follows early alcohol use, and any other relevant factors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known financial or personal interests to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Background: Adolescents and young adults may use cannabidiol (CBD) products in an attempt to reduce depression and anxiety symptoms, despite little research examining this use. This systematic review evaluated preclinical and clinical research on the effects of CBD on depressive and anxiety disorders in adolescence and young adulthood. To provide context, we discuss CBD's mechanism of action and neurodevelopmental effects., Methods: PubMed was searched for articles published through June 2022. Preclinical or clinical CBD administration studies with N > 1 that examined depressive and/or anxiety disorders were eligible., Results: Initially, 224 publications were identified. After excluding duplicates and applying eligibility criteria, 6 preclinical (depression: n ≈133; anxiety: n ≈161) and 4 clinical (anxiety: n =113) articles remained. Due to the low number of studies, results were synthesized qualitatively. The Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence were used to rate each study's evidence. The preclinical effects of CBD on depression-like behavior appear to differ by sex, early life stress, and duration of use. Despite no evidence that CBD exerts anxiolytic effects in preclinical adolescent models, CBD may reduce anxiety symptoms in human adolescents and young adults with anxiety disorders., Conclusions: The existing evidence suggests that CBD may reduce symptoms of anxiety in adolescents and young adults. However, the evidence is sparse and limited by variations in samples and CBD dosing duration. Further research is needed to understand the potential benefits and/or harms of CBD for depression and anxiety disorders in this population. Implications for clinical practice and research are discussed., Competing Interests: NAC, RKD, and JB have no conflicts of interest to report. GP is a paid consultant to PureTech Health (Boston, MA, USA), GABA Therapeutics, and NeuroTrauma Sciences (Alpharetta, GA, USA). He has two patent applications, one on N-palmitoylethanolamine (PEA) and peroxisome proliferator-activated receptor alpha (PPAR-α) agonists US20180369171A1, pending, and one on allopregnanolone analogs in the treatment of neuropsychiatric disorders (US11266663B2, granted on March 8, 2022).

The reward positivity (RewP) event-related potential is a well-validated measure of reward processing implicated in internalizing psychopathologies. The RewP is thought to reflect reward reactivity in the mesocorticolimbic system; however, it is not clear how the RewP is related to the functional connectivity of reward-related brain regions. The current study examined associations between the RewP (Win and Loss residuals) and resting-state fMRI (rs-fMRI), among adults with internalizing psychopathology (IP) and healthy controls (HC). All participants (N = 102) completed a validated monetary reward task during electroencephalogram and rs-fMRI. Regression analyses were conducted with (1) RewP-Win residual amplitude and striatal seeds (caudate, putamen, nucleus accumbens) and (2) RewP-Loss residual amplitude and anterior cingulate cortex (ACC) seeds. Overall, individuals with greater RewP-Win residual amplitude demonstrated increased rs-fMRI connectivity between striatal regions and the medial prefrontal cortex, as well as the parahippocampal gyrus, but decreased connectivity between striatal regions and regions involved in cognitive control and sensorimotor processing. Greater RewP-Loss residual was related to greater connectivity between the ACC and regions involved in reward/loss processing and motor control, but decreased connectivity between the ACC and regions involved in cognitive control. Relationships between the RewP and rs-fMRI were generally consistent across IP and HC. However, a few patterns were unique to IP. Results indicate the RewP is associated with resting-state functional connectivity of reward- and loss-related brain regions, suggesting connectivity of the mesocorticolimbic system may be an important individual difference factor in dimensions of attainment of reward and loss., (© 2022 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Introduction: Alcohol, nicotine, and marijuana are the three most widely used substances among adolescents and young adults, with co-use of multiple substances being common. Few longitudinal studies have examined risk factors of alcohol, marijuana, and nicotine poly-substance use. We examined frequency of alcohol, marijuana, and cigarette poly-substance use over time and how key risk factors contribute to this substance use during adolescence and young adulthood., Methods: Participants (N = 1263 9th and 10th graders) were oversampled for ever-smoking a cigarette at baseline from 16 Chicago-area high schools between 2004 and 2006. Many participants progressed to heavier cigarette use, as well as alcohol and marijuana use over time. Participants completed questionnaires assessing substance use and psychosocial factors at baseline, 6-, 15-, 24-, 33-months, and 5-, 6-, and 7-years., Results: Longitudinal multi-level models demonstrated that at baseline and over time, more depression symptoms, more anxiety symptoms, negative mood regulation expectancies, and lower grade point average (GPA) were each associated with more poly-substance use over time. In addition, there were a number of interaction effects of gender (e.g., depression was related to substance use in males) and developmental stage moderated these relationships., Conclusions: Depression, anxiety, negative mood regulation expectancies, and GPA all significantly influence both initial and longitudinal levels of substance use across adolescence and young adulthood. Our findings underscore the importance of identifying and treating youth with depression and anxiety symptoms, as well as providing resources early for those struggling in school in order to help with substance use prevention and intervention efforts., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Few studies have examined how Δ9-Tetrahydrocannabinol (THC), the main psychoactive component of cannabis, impacts brain reward circuitry in humans. In this study, we examined if an acute dose of THC altered resting state functional connectivity between the striatum and prefrontal cortex among healthy young adults with limited cannabis use., Methods: Participants received THC (n = 24) or placebo (n = 22) in a double-blind, randomized, between-subject design. Participants completed self-report measures of euphoria and drug-liking throughout the visit. Approximately 120 min after drug administration, participants completed an 8-min resting state functional MRI (rs-fMRI) scan. We utilized seed-based connectivity of the striatum (bilateral putamen, caudate, and NAcc seeds) to the frontal cortex., Results: Individuals who received THC demonstrated greater rs-fMRI connectivity between the right NAcc and regions of the medial prefrontal cortex (mPFC) (p-values<0.05, corrected) and higher subjective euphoria ratings (p = .03) compared to compared to individuals who received placebo. Higher ratings of euphoria were related to greater right NAcc-dorsal mPFC (dmPFC) connectivity for the THC group (p=.03), but not for the placebo group (p=.98)., Conclusions: This is one of the first studies to examine rs-fMRI connectivity in healthy young non-users after THC administration. We found individuals receiving THC show greater rs-fMRI connectivity between the NAcc and mPFC, regions implicated in reward, compared to individuals receiving placebo. In addition, individuals receiving THC reported higher subjective euphoria ratings, which were positively associated with NAcc-dmPFC connectivity. Overall, our findings suggest THC may produce subjective and neural reward responses that contribute to the rewarding, reinforcing properties of cannabis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Disruptions in neural measures of reward responsiveness are implicated in risk for and the development of Substance Use Disorders (SUDs) in general, but it is not clear if this is also true for Cannabis Use Disorder (CUD). To date, no studies have examined neural reward responsiveness in cannabis users using EEG., Methods: Cannabis users (CU; n = 67) and non-users (n = 60) were drawn from larger studies of individuals with and without internalizing and externalizing psychopathology. Groups were matched on current and lifetime psychopathology. Participants completed a validated monetary reward task during electroencephalogram (EEG). One-way between subject analysis of covariance (ANCOVA) models examined group differences in four EEG indicators of reward responsiveness - the reward positivity (RewP) and feedback negativity (FN) event-related potentials and two time-frequency measures (reward-related delta and loss-related theta)., Results: CU demonstrated an enhanced RewP to the attainment of monetary reward compared to non-users (p = .004), even after controlling for relevant covariates. Secondary analyses found that occasional CU, but not current CUD or remitted CUD, showed enhanced RewP compared to non-users. There were no significant differences in FN, reward-related delta, or loss-related theta time-frequency measures between groups., Conclusions: To our knowledge, this is the first study to show preliminary evidence that CU have an enhanced RewP to reward and the extent of disruption may be related to CUD status. Our findings suggest that greater neural reward responsiveness may only be seen among occasional CU, not necessarily among CU with current or remitted CUD., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

One well-known phenotypic risk factor for the development of alcohol use disorder is sensitivity to the rewarding effects of alcohol. In the present study, we examined whether individuals who are sensitive to alcohol reward are also sensitive to nondrug rewards, thereby reflecting a broader individual difference risk factor. Specifically, we tested the hypothesis that subjective response to acute rewarding effects of alcohol would be related to neural activation during monetary reward receipt relative to loss (in the absence of alcohol). Community-recruited healthy young social drinkers (N = 58) completed four laboratory sessions in which they received alcohol (0.8 g/kg) and placebo in alternating order under double-blind conditions, providing self-report measures of subjective response to alcohol at regular intervals. At a separate visit 1-3 weeks later, they completed a reward-guessing game, the 'Doors' task, during fMRI in a drug-free state. Participants who reported greater motivation (i.e., wanting) to consume more alcohol after a single moderate dose of alcohol also exhibited greater neural activation in the bilateral ventral caudate and the nucleus accumbens during reward receipt relative to loss. Striatal activation was not related to other subjective ratings including alcohol-induced sedation, stimulation, or pleasure (i.e., feeling, liking). Our study is the first to show that measures of alcohol reward are related to neural indices of monetary reward in humans. These results support growing evidence that individual differences in responses to drug and nondrug reward are linked and together form a risk profile for drug use or abuse, particularly in young adults.

Social anxiety disorder (SAD) is a common heterogeneous disorder characterized by excessive fear and deficient positive experiences. Case-control emotion processing studies indicate that altered amygdala and striatum function may underlie SAD; however, links between these regions and symptomatology have yet to be established. Therefore, in the current study, 80 individuals diagnosed with SAD completed a validated emotion processing task during functional magnetic resonance imaging. Anatomy-based regions of interest were amygdala, caudate, putamen, and nucleus accumbens. Neural activity in response to angry > happy faces and fearful > happy faces in these regions were submitted to multiple linear regression analysis with bootstrapping. Additionally, multiple linear regression analysis was performed to explore clinical features of SAD. Results showed greater putamen activity and less amygdala activity in response to angry > happy faces were related to greater social anxiety severity. In the model consisting of caudate and amygdala activity in response to angry > happy faces, results were marginally related to social anxiety severity and the pattern of activity was similar to the regression model comprising putamen and amygdala. Nucleus accumbens activity was not related to social anxiety severity. There was no correspondence between brain activity in response to fearful > happy faces and social anxiety severity. Clinical variables revealed greater levels of anhedonia and general anxiety were related to social anxiety severity, however, neural activity was not related to these features of SAD. Neuroimaging findings suggest that variance in dorsal striatal and amygdala activity in response to certain social signals of threat contrasted with an approach/rewarding social signal may contribute to individual differences in SAD. Clinical findings indicate variance in anhedonia and general anxiety symptoms may contribute to individual differences in social anxiety severity., (Copyright © 2021. Published by Elsevier Inc.)

Background: Alcohol use disorder (AUD) remains an unresolved source of morbidity and mortality. Psychopharmacological challenge studies and neuroimaging experiments are two methods used to identify risk of problematic substance use. The present study combined these two approaches by examining associations between self-reported stimulation, sedation, liking or wanting more after a dose of alcohol and neural-based responses to anticipation of monetary gain and loss., Methods: Young adult binge drinkers (N = 56) aged 21-29, with no history of Substance Use Disorder completed five experimental sessions. These included four laboratory sessions in which they rated their subjective responses to alcohol (0.8 g/kg for men, 0.68 g/kg for women) or placebo, and a single functional magnetic resonance imaging session in which they completed a monetary incentive delay task. During the scan, we recorded neural signal related to anticipation of winning $5 or $1.50 compared to winning no money (WinMoney-WinZero), losing $5 or $1.50 compared to losing no money (LoseMoney-LoseZero), and winning $5 or $1.50 compared to losing $5 or $1.50 (WinMoney-LoseMoney), in reward related regions., Results: There were no significant associations between subjective ratings of "Feel Drug Effect", "Like Drug Effect", "Want More", stimulation or sedation following the acute alcohol challenge and neural activation in reward related regions during anticipation of monetary gain or loss., Conclusions: These results suggest that sensitivity of neural reward circuits is not directly related to rewarding subjective experiences from alcohol. Taken together with previous studies, the present findings indicate that the association between the subjective effects of drugs and reward-related brain activity depends on the drugs, tasks or subject samples under study., (Published by Elsevier B.V.)

The cognitive processes involved in inhibitory control accuracy (IC) and interference resolution speed (IR) or broadly - inhibition - are discussed in this review, and both are described within the context of a lifespan model of mood disorders. Inhibitory control (IC) is a binary outcome (success or no for response selection and inhibition of unwanted responses) for any given event that is influenced to an extent by IR. IR refers to the process of inhibition, which can be manipulated by task design in earlier and later stages through use of distractors and timing, and manipulation of individual differences in response proclivity. We describe the development of these two processes across the lifespan, noting factors that influence this development (e.g., environment, adversity and stress) as well as inherent difficulties in assessing IC/IR prior to adulthood (e.g., cross-informant reports). We use mood disorders as an illustrative example of how this multidimensional construct can be informative to state, trait, vulnerability and neuroprogression of disease. We present aggregated data across numerous studies and methodologies to examine the lifelong development and degradation of this subconstruct of executive function, particularly in mood disorders. We highlight the challenges in identifying and measuring IC/IR in late life, including specificity to complex, comorbid disease processes. Finally, we discuss some potential avenues for treatment and accommodation of these difficulties across the lifespan, including newer treatments using cognitive remediation training and neuromodulation.

Trait markers, or intermediate phenotypes linking different units of analysis (self-report, performance) from the Research Domain Criteria (RDoC) matrix across populations is a necessary step in identifying at-risk individuals. In the current study, 150 healthy controls (HC) and 456 individuals with bipolar disorder (BD) Type I or II, NOS (not otherwise specified) or Schizoaffective BD completed self-report neuropsychological tests of inhibitory control (IC) and executive functioning. Bifactor analyses were used to examine the factor structure of these measures and to evaluate for invariance across groups. Bifactor analyses found modest convergence of items from neuropsychological tests and self-report measures of IC among HC and BD. The factor scores showed evidence of a general IC construct (i.e., subdomain) across measures. Importantly, invariance testing indicated that the same construct was measured equally well across groups. Groups differed on the general factor for three of the four scales. Convergence on a general IC factor and invariance across diagnosis supports the use of combined dimensional measures to identify clinical risk and highlights how prospective RDoC studies might integrate units of analysis.

Background: Drug addiction and dependence continue as an unresolved source of morbidity and mortality. Two approaches to identifying risk for abuse and addiction are psychopharmacological challenge studies and neuroimaging experiments. The present study combined these two approaches by examining associations between self-reported euphoria or liking after a dose of d-amphetamine and neural-based responses to anticipation of a monetary reward., Methods: Healthy young adults (N = 73) aged 19 and 26, without any history of alcohol/substance dependence completed four laboratory sessions in which they received oral d-amphetamine (20 mg) or placebo, and completed drug effect questionnaires. On a separate session they underwent a functional magnetic resonance imaging scan while they completed a monetary incentive delay task. During the task, we recorded neural signal related to anticipation of winning $5 or $1.50 compared to winning no money (WinMoney-WinZero), in reward related regions., Results: Liking of amphetamine during the drug sessions was related to differences in activation during the WinMoney-WinZero conditions - in the amygdala (positive), insula (negative) and caudate (negative). In posthoc analyses, liking of amphetamine was also positively correlated with activation of the amygdala during anticipation of large rewards and negatively related to activation of the left insula to both small and large anticipated rewards., Conclusions: These findings suggest that individual differences in key regions of the reward network are related to rewarding subjective effects of a stimulant drug. To further clarify these relationships, future pharmacofMRI studies could probe the influence of amphetamine at the neural level during reward anticipation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Individuals with impulsive and addictive disorders, including drug addiction, binge eating/obesity, and problem gambling, exhibit both impaired control over behavior and heightened sensitivity to reward. However, it is not known whether such deviation in inhibitory and reward circuitry among clinical populations is a cause or consequence of the disorders. Recent evidence suggests that these constructs may be related at the neural level, and together, increase risk for engaging in maladaptive behaviors. The current study examined the degree to which brain function during inhibition relates to brain function during receipt of reward in healthy young adults who have not yet developed problem behaviors. Participants completed the stop signal task to assess inhibitory control and the doors task to assess reactivity to monetary reward (win vs loss) during functional magnetic resonance imaging (fMRI). Brain activation during response inhibition was negatively correlated with brain activation during reward. Specifically, less brain activation in right prefrontal regions during inhibition, including the right inferior frontal gyrus, middle frontal gyrus, and supplementary motor area, was associated with greater brain activation in left ventral striatum during receipt of monetary reward. Moreover, these associations were stronger in binge drinkers compared to non-binge drinkers. These findings suggest that the systems are related even before the onset of impulsive or addictive disorders. As such, it is possible that the association between inhibitory and reward circuitry may be a prospective marker of risk., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A large number of studies have attempted to use neuroimaging tools to aid in treatment prediction models for major depressive disorder (MDD). Most such studies have reported on only one dimension of function and prediction at a time. In this study, we used three different tasks across domains of function (emotion processing, reward anticipation, and cognitive control, plus resting state connectivity completed prior to start of medication to predict treatment response in 13-36 adults with MDD. For each experiment, adults with MDD were prescribed only label duloxetine (all experiments), whereas another subset were prescribed escitalopram. We used a KeyNet (both Task derived masks and Key intrinsic Network derived masks) approach to targeting brain systems in a specific match to tasks. The most robust predictors were (Dichter et al., 2010) positive response to anger and (Gong et al., 2011) negative response to fear within relevant anger and fear TaskNets and Salience and Emotion KeyNet (Langenecker et al., 2018) cognitive control (correct rejections) within Inhibition TaskNet (negative) and Cognitive Control KeyNet (positive). Resting state analyses were most robust for Cognitive control Network (positive) and Salience and Emotion Network (negative). Results differed by whether an -fwhm or -acf (more conservative) adjustment for multiple comparisons was used. Together, these results implicate the importance of future studies with larger sample sizes, multidimensional predictive models, and the importance of using empirically derived masks for search areas., (Copyright © 2018. Published by Elsevier Inc.)

Background: Three well-established intrinsic connectivity networks (ICNs) involved in cognitive-affective processing include the cognitive control network (CCN), default mode network (DMN), and salience and emotional network (SEN). Despite recent advances in understanding developmental changes in these ICNs, the majority of research has focused on single seeds or networks in isolation with limited age ranges. Additionally, although internalizing psychopathologies (IPs), such as anxiety and depression, are often characterized by maladaptive cognitive-affective processing styles, it is not clear how IP history influences age-related changes in brain networks., Method: The current study aimed to characterize the normative development of the CCN, DMN, and SEN across a large age-span (7-29 year olds) of typically developing (TD) individuals (n = 97). We also explore how age may impact differences in network connectivity between TD individuals and patients with IPs (n = 136)., Results: Among TD individuals, DMN and CCN connectivity strengthened with age, whereas connectivity between the SEN and ventromedial prefrontal cortex weakened across development. When exploring group (IP vs. TD) differences, the IP group was characterized by greater connectivity between the CCN and cerebellum and between the SEN and caudate from childhood to early adulthood, relative to TD individuals. In addition, patients with IPs, versus TD individuals, exhibited reduced connectivity between the SEN and medial frontal gyrus from adolescence to adulthood., Conclusions: The current findings shed light on differential age-related changes in brain network patterns among psychiatrically free, TD individuals and those with internalizing disorders, and may provide plausible targets for novel mechanism-based treatments that differ based on developmental stage., (© 2018 Wiley Periodicals, Inc.)

Background: Major depressive disorder (MDD) and anxiety disorders are highly comorbid, sharing many similar symptoms, including impairments in cognitive control. Deficits in cognitive control could be a potential mechanism underlying impaired emotion regulation in mood disorders., Methods: Participants were 44 individuals with no history of mental illness (healthy controls, HC), 31 individuals in the remitted state of MDD (rMDD), and 18 individuals who met lifetime DSM-IV-TR criteria for rMDD and an anxiety disorder in remission (Comorbid). Participants completed a Parametric Go/No-Go (PGNG) test during fMRI. Event-related analyses modeled activity for cognitive control successes (Hits for Targets, Rejections for Lures) and failures (Commissions on Lures) on the PGNG task., Results: The rMDD group showed significantly reduced activity within the cognitive control network (CCN) during Commission errors, including the middle frontal gyrus and inferior parietal lobule (IPL). The Comorbid group showed significantly reduced activity in several clusters within the CCN during correct Rejections, including the left IPL and right inferior frontal gyrus and greater subgenual cingulate. Notably, during correct Rejections, 60% of activation for the Comorbid group was within the Salience and Emotion Network (SEN), with 0% within the CCN., Limitations: The size of the Comorbid subgroup was modest, preventing subanalysis of the different AD subtypes., Conclusions: There is evidence that CCN activity declines in rMDD and that there may be compensatory SEN activity in individuals with Comorbid rMDD and anxiety. Our findings support the identification of comorbid anxiety as a meaningful subtype of MDD that may obscure group differences between rMDD and HCs., (Copyright © 2018. Published by Elsevier B.V.)

Cannabis use is prevalent but only a minority of regular users develop cannabis use disorder (CUD); thus, CUD risk identification among current cannabis users is vital for targeted intervention development. Existing data suggest that high distress intolerance (DI), an individual difference reflective of the ability to withstand negative affect, is linked to CUD, possibly via stress-elicited impairment of response inhibition but this has never been explicitly tested. Frequent cannabis users with high and low DI completed a go/no-go task during EEG recording before and after a laboratory stressor. Relations between DI, cannabis use-related problems, and behavioral as well as neurophysiological markers of response inhibition functioning were assessed. DI significantly moderated the effect of the stressor on the conflict-monitoring but not evaluative phase of response inhibition as measured by N2 and P3a amplitude, respectively. Unexpectedly, cannabis users with high DI demonstrated stressor-elicited enhancement rather than impairment of conflict-monitoring neural activity, which was related to faster reaction time (RT) and decreased past-month cannabis problems. Enhanced inhibition-related modulation of P3a amplitude was generally associated with increased cannabis problems regardless of acute stress. Results did not provide support for stress-elicited impairment in cognitive control as a mechanism linking high DI and CUD, though some support was found for the relevance of inhibition-related neural activity to CUD. Stress-elicited enhancement of conflict-monitoring neural activity during response inhibition may reflect an adaptive neural response among cannabis users with high DI that protects against CUD in this at-risk group. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Background: Decreased amygdala-orbitofrontal cortex (OFC) neural functional connectivity (FC) positively predicts alcohol use among adolescents. Low amygdala-OFC FC is also associated with poor emotion regulation, a trait robustly linked to alcohol use. Thus, decreased amygdala-OFC connectivity may represent a risk factor for the development of alcohol use disorder (AUD) via impaired emotion regulation or reward processing. In this study, we examined amygdala-OFC FC among young adult binge drinkers at high risk for AUD. We also tested if amygdala-OFC FC mediates the relationship between externalizing personality traits and alcohol use., Methods: Healthy male and female (n = 39) binge drinkers completed a resting state fMRI scan and the Eysenck Impulsive Personality questionnaire. We utilized seed-based connectivity of the left and right amygdala to prefrontal regions as well as mediation analysis., Results: Individuals with higher weekly alcohol use displayed decreased right amygdala-OFC FC. Furthermore, high trait venturesomeness, but not impulsivness, was associated with decreased right amygdala-OFC FC. Finally, right amygdala-OFC FC mediated the relationship between trait venturesomeness and weekly drinking; individuals with high trait venturesomeness displayed decreased right amygdala-OFC FC, which in turn predicted greater weekly drinking., Conclusions: Our findings corroborate and extend the adolescent literature by showing that decreased amygdala-OFC FC is associated with higher alcohol consumption among adults at elevated risk for AUD. This study also demonstrates for the first time that this neural profile reflects a tendency to sensation seeking. In sum, our findings suggest that amygdala-OFC FC may be an objective neural target for alcohol use prevention and intervention., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Rates of comorbid alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are increasing among post-9/11 veterans, and emotion regulation problems have been identified as a feature of both disorders. However, no studies to date have explored how individual differences in emotion regulation may moderate the relationship between PTSD symptoms and alcohol use. We evaluated how two core emotion regulation strategies - one adaptive (i.e., cognitive reappraisal) and one maladaptive (i.e., expressive suppression) are related to PTSD symptoms and alcohol use over one-year., Methods: A total of 71 post-9/11 veterans (12 female, 59 male) completed a baseline screening and at least two follow-up assessments over the course of 12 months which included measures of emotion regulation, PTSD symptoms, and alcohol use. A mixed growth model was utilized to determine if changes in PTSD symptoms covaried with alcohol use over time and whether this relation was moderated by frequency of use of emotion regulation strategies., Results: In general, higher PTSD symptoms were significantly associated with greater alcohol use, but cognitive reappraisal moderated this relationship. Specifically, at low cognitive reappraisal, greater PTSD symptoms were associated with greater alcohol use. At high cognitive reappraisal, there was no significant association between PTSD symptoms and alcohol use., Conclusions: Findings from the present study suggest that baseline individual differences in cognitive reappraisal influence the relation between PTSD symptoms and alcohol use. For post-9/11 veterans, high levels of cognitive reappraisal may serve as a protective factor against ongoing alcohol use., (Copyright © 2018 Elsevier B.V. All rights reserved.)

One known risk factor for drug use and abuse is sensitivity to rewarding effects of drugs. It is not known whether this risk factor extends to sensitivity to non-drug rewards. In this study with healthy young adults, we examined the association between sensitivity to the subjective rewarding effects of amphetamine and a neural indicator of anticipation of monetary reward. We hypothesized that greater euphorigenic response to amphetamine would be associated with greater neural activation to anticipation of monetary reward (Win > Loss). Healthy participants (N = 61) completed four laboratory sessions in which they received d-amphetamine (20 mg) and placebo in alternating order, providing self-report measures of euphoria and stimulation at regular intervals. At a separate visit 1-3 weeks later, participants completed the guessing reward task (GRT) during fMRI in a drug-free state. Participants reporting greater euphoria after amphetamine also exhibited greater neural activation during monetary reward anticipation in mesolimbic reward regions, including the bilateral caudate and putamen. This is the first study to show a relationship between neural correlates of monetary reward and sensitivity to the subjective rewarding effects of amphetamine in humans. These findings support growing evidence that sensitivity to reward in general is a risk factor for drug use and abuse, and suggest that sensitivity of drug-induced euphoria may reflect a general sensitivity to rewards. This may be an index of vulnerability for drug use or abuse.

Purpose of Review: We set out to review the current state of science in neuroprediction, using biological measures of brain function, with task based fMRI to prospectively predict response to a variety of treatments., Recent Findings: Task-based fMRI neuroprediction studies are balanced between whole brain and ROI specific analyses. The predominant tasks are emotion processing, with ROIs based upon amygdala and subgenual anterior cingulate gyrus, both within the salience and emotion network. A rapidly emerging new area of neuroprediction is of disease course and illness recurrence. Concerns include use of open-label and single arm studies, lack of consideration of placebo effects, unbalanced adjustments for multiple comparisons (over focus on type I error), small sample sizes, unreported effect sizes, overreliance on ROI studies., Summary: There is a need to adjust neuroprediction study reporting so that greater coherence can facilitate meta analyses, and increased funding for more multiarm studies in neuroprediction., Competing Interests: Conflicts of Interest The authors have received grant money from the National Institute of Mental Health.

Background: Currently, we do not have biomarkers to help identify individuals at-risk for chronic, problematic alcohol use, especially among veteran populations, who have notoriously high rates of alcohol use. One biomarker that may predict individuals at risk for chronic, problematic alcohol use is error-related brain activity. We examined longitudinal associations between the error-related negativity (ERN), an event-related potential observed following the commission of errors, and problematic alcohol use among U.S. military veterans returning from recent conflicts in Iraq and Afghanistan., Methods: Forty-six military veterans, aged 18-55 years, completed a well-validated flanker task known to elicit the ERN at baseline. Problematic alcohol use and other clinically relevant variables were assessed at baseline, 3-, 6-, 9-, 12-, 15-, 18-, 21-months, and 2 years., Results: Results indicated that the ERN magnitude was associated with problematic alcohol use over time, even after controlling for relevant clinical variables. Specifically, veterans with a smaller ERN magnitude evidenced a decline in problematic alcohol use over time, while veterans with a larger ERN magnitude had no change in their problematic alcohol use across the follow-up. In addition, exploratory analyses found that treatment engagement during the study did not moderate these relationships., Conclusions: Our findings provide preliminary evidence that ERN can be used as a predictor of problematic alcohol use over time. Therefore, neural response to errors could help to identify individuals at risk for continued problematic alcohol use for intervention efforts and suggests that error processing may be an important therapeutic target within Alcohol Use Disorder intervention efforts., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aims: Dysfunctional brain reward circuitry, particularly in the nucleus accumbens (NAcc), has been proposed as a risk factor for alcohol use disorder (AUD). This risk factor may be evident in binge drinkers (BD), who are at high risk for developing AUD. We examined whole-brain and NAcc reactivity to reward in BD compared to non-binge drinkers (NBD), hypothesizing that groups would differ in their neural reactivity and connectivity., Methods: Healthy BD (N = 27) and NBD (N = 23)-none meeting AUD criteria-completed a reward-guessing game, the 'Doors' task, during functional magnetic resonance imaging. We conducted an exploratory whole-brain search for group differences, but given our a priori hypotheses, we also extracted activation from the NAcc to examine reactivity during reward (Win > Loss) and functional connectivity (FC) to the prefrontal cortex., Results: Compared to NBD, BD exhibited greater activation in both the right and left NAcc during reward relative to loss. Additionally, NBD drinkers exhibited positive FC between the NAcc and dorsal anterior cingulate (dACC) whereas the BD showed negative FC between these regions. Furthermore, less NAcc-dACC FC was related to more past month alcohol use., Conclusions: Our results provide preliminary evidence that BD exhibit greater NAcc activation during reward receipt relative to loss. This is consistent with the broader AUD literature and suggests aberrant neural reactivity may precede disorder onset. In addition, BD exhibited less NAcc-dACC FC, perhaps reflecting deficient regulation of activation to rewards compared to losses. This profile of reward brain circuitry could represent neural correlates of vulnerability for AUD., Short Summary: Healthy binge drinkers, at risk for alcohol use disorder, exhibited greater nucleus accumbens activation during reward relative to loss. In addition, binge drinkers exhibited reduced connectivity between the nucleus accumbens and dorsal anterior cingulate, which was associated with more past month alcohol use., (© The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Introduction: Studying remitted Major Depressive Disorder (rMDD) facilitates a better understanding of neural mechanisms for risk, given that confounding effects of active symptoms are removed. Disrupted functional connectivity has been reported in multiple networks in MDD. However, no study to date of rMDD has specifically examined connectivity of the ventral striatum (VS), a region highly implicated in reward and motivation. We investigated functional connectivity of the VS in individuals with and without a history of MDD, and in relation to affective personality traits., Methods: Forty-two individuals with rMDD and 28 healthy controls across two sites completed resting-state fMRI and the Behavioral Inhibition System/Behavioral Activation System Scale. Voxel-wise, whole-brain comparisons were conducted across and between groups for four seeds: left and right inferior VS (VSi), left and right superior VS (VSs)., Results: VSs connectivity to temporal and subcortical regions including the putamen and amygdala was positive and greater in HCs compared to rMDD individuals. Across groups, VSi connectivity was positively correlated with trait reward-responsiveness in somatomotor regions. Across groups, VSs connectivity was positively correlated with trait drive, particularly in the putamen, parahippocampal, and inferior temporal gyrus, and was negatively associated with trait behavioral inhibition in the anterior cingulate, frontal gyri, and insula., Limitations: Limitations include scanning at two sites and using multiple comparisons., Discussion: Group connectivity differences emerged from the VSs rather than VSi. VSs showed associations with trait drive and behavioral inhibition, whereas VSi corrrelated with reward-responsiveness. Depression history and affective traits contribute meaningful and specific information about VS connectivity in understanding risk for MDD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aim: Impairment in neuropsychological functioning is common in major depressive disorder (MDD), but it is not clear to what degree these deficits are related to risk (e.g. trait), scar, burden or state effects of MDD. The objective of this study was to use neuropsychological measures, with factor scores in verbal fluency, processing speed, attention, set-shifting and cognitive control in a unique population of young, remitted, unmedicated, early course individuals with a history of MDD in hopes of identifying putative trait markers of MDD., Methods: Youth aged 18-23 in remission from MDD (rMDD; n = 62) and healthy controls (HC; n = 43) were assessed with neuropsychological tests at two time points. These were from four domains of executive functioning, consistent with previous literature as impaired in MDD: verbal fluency and processing speed, conceptual reasoning and set-shifting, processing speed with interference resolution, and cognitive control., Results: rMDD youth performed comparably to HCs on verbal fluency and processing speed, processing speed with interference resolution, and conceptual reasoning and set-shifting, reliably over time. Individuals with rMDD demonstrated relative decrements in cognitive control at Time 1, with greater stability than HC participants., Conclusion: MDD may be characterized by regulatory difficulties that do not pertain specifically to active mood state or fluctuations in symptoms. Deficient cognitive control may represent a trait vulnerability or early course scar of MDD that may prove a viable target for secondary prevention or early remediation., (© 2015 Wiley Publishing Asia Pty Ltd.)

We introduce a chemical sensing technology, named ChIMES (Chemical Identification through Magneto-Elastic Sensing), that can detect a broad range of targets and that has the capability of untethered communication through a metallic or nonmetallic barrier. These features enable many applications in which penetrations into the sampled environment are unwanted or infeasible because of health, safety, or environmental concerns, such as following the decomposition of a dangerous material in a sealed container. The sensing element is passive and consists of a target response material hard-coupled to a magnetoelastic wire. When the response material encounters a target, it expands, imposing mechanical stress on the wire and altering its magnetic permeability. Using a remote excitation-detection coil set, the changes in permeability are observed by switching the magnetic domains in the wire and measuring the modifications in the Faraday voltage as the stress is varied. Sensors with different response materials can be arrayed and interrogated individually. We describe the sensor and its associated instrumentation, compare the performance of several types of wire, and evaluate analytical metrics of single and arrayed ChIMES sensors against a suite of volatile organic compounds.

Many individuals with major depressive disorder (MDD) experience cognitive dysfunction including impaired cognitive control and negative cognitive styles. Functional connectivity magnetic resonance imaging studies of individuals with current MDD have documented altered resting-state connectivity within the default-mode network and across networks. However, no studies to date have evaluated the extent to which impaired connectivity within the cognitive control network (CCN) may be present in remitted MDD (rMDD), nor have studies examined the temporal stability of such attenuation over time. This represents a major gap in understanding stable, trait-like depression risk phenotypes. In this study, resting-state functional connectivity data were collected from 52 unmedicated young adults with rMDD and 47 demographically matched healthy controls, using three bilateral seeds in the CCN (dorsolateral prefrontal cortex, inferior parietal lobule, and dorsal anterior cingulate cortex). Mean connectivity within the entire CCN was attenuated among individuals with rMDD, was stable and reliable over time, and was most pronounced with the right dorsolateral prefrontal cortex and right inferior parietal lobule, results that were corroborated by supplemental independent component analysis. Attenuated connectivity in rMDD appeared to be specific to the CCN as opposed to representing attenuated within-network coherence in other networks (e.g., default-mode, salience). In addition, attenuated connectivity within the CCN mediated relationships between rMDD status and cognitive risk factors for depression, including ruminative brooding, pessimistic attributional style, and negative automatic thoughts. Given that these cognitive markers are known predictors of relapse, these results suggest that attenuated connectivity within the CCN could represent a biomarker for trait phenotypes of depression risk. Hum Brain Mapp 38:2939-2954, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Predicting treatment response for major depressive disorder can provide a tremendous benefit for our overstretched health care system by reducing number of treatments and time to remission, thereby decreasing morbidity. The present study used neural and performance predictors during a cognitive control task to predict treatment response (% change in Hamilton Depression Rating Scale pre- to post-treatment). Forty-nine individuals diagnosed with major depressive disorder were enrolled with intent to treat in the open-label study; 36 completed treatment, had useable data, and were included in most data analyses. Participants included in the data analysis sample received treatment with escitalopram (n = 22) or duloxetine (n = 14) for 10 weeks. Functional MRI and performance during a Parametric Go/No-go test were used to predict per cent reduction in Hamilton Depression Rating Scale scores after treatment. Haemodynamic response function-based contrasts and task-related independent components analysis (subset of sample: n = 29) were predictors. Independent components analysis component beta weights and haemodynamic response function modelling activation during Commission errors in the rostral and dorsal anterior cingulate, mid-cingulate, dorsomedial prefrontal cortex, and lateral orbital frontal cortex predicted treatment response. In addition, more commission errors on the task predicted better treatment response. Together in a regression model, independent component analysis, haemodynamic response function-modelled, and performance measures predicted treatment response with 90% accuracy (compared to 74% accuracy with clinical features alone), with 84% accuracy in 5-fold, leave-one-out cross-validation. Convergence between performance markers and functional magnetic resonance imaging, including novel independent component analysis techniques, achieved high accuracy in prediction of treatment response for major depressive disorder. The strong link to a task paradigm provided by use of independent component analysis is a potential breakthrough that can inform ways in which prediction models can be integrated for use in clinical and experimental medicine studies., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Major Depressive Disorder (MDD) and anxiety disorders often co-occur, with poorer treatment response and long-term outcomes. However, little is known about the shared and distinct neural mechanisms of comorbid MDD and anxiety (MDD+Anx). This study examined how MDD and MDD+Anx differentially impact cognitive control., Methods: Eighteen MDD, 29 MDD+Anx, and 54 healthy controls (HC) completed the Parametric Go/No-Go (PGNG) during fMRI, including Target, Commission, and Rejection trials., Results: MDD+Anx had more activation in the anterior dorsolateral prefrontal cortex, hippocampus, and caudate during Rejections, and inferior parietal lobule during correct Targets than MDD and HC. During Rejections HC had greater activation in a number of cognitive control regions compared to MDD; in the posterior cingulate compared to MDD+Anx; and in the fusiform gyrus compared to all MDD. During Commissions HC had greater activation in the right inferior frontal gyrus than all MDD. MDD had more activation in the mid-cingulate, inferior parietal lobule, and superior temporal gyrus than MDD+Anx during Commissions., Conclusions: Despite similar performance, MDD and MDD+Anx showed distinct differences in neural mechanisms of cognitive control in relation to each other, as well as some shared differences in relation to HC. The results were consistent with our hypothesis of hypervigilance in MDD+Anx within the cognitive control network, but inconsistent with our hypothesis that there would be greater engagement of salience and emotion network regions. Comorbidity of depression and anxiety may cause increased heterogeneity in study samples, requiring further specificity in detection and measurement of intermediate phenotypes and treatment Targets., Competing Interests: SAL reports consulting work with Easter Seals, Inc. that was not related to the study. The authors declare no other real or potential conflicts of interest., (© 2016 Wiley Periodicals, Inc.)

Introduction: Vulnerability factors like respiratory sinus arrhythmia (RSA) may help identify adolescents at risk for nicotine dependence. We examined if resting RSA and the acute effects of smoking on RSA was associated with cigarette smoking five years later among adolescents at high risk for smoking escalation and nicotine dependence., Methods: Sixty-nine adolescents participated in a baseline laboratory session- RSA was collected before and after smoking a single cigarette ad libitum. Participants were then followed for five years., Results: Lower pre-smoke resting RSA was related to higher past month smoking rate five years later, even after controlling for baseline smoking rate and other relevant covariates including gender, race/ethnicity, age of initiated use, and frequency of exercise at baseline (p=0.018). Exploratory analyses suggested resting RSA is an independent predictor of increased cigarette rate beyond other baseline predictors., Conclusions: Low resting RSA may be a vulnerability factor, helping to identify adolescents at risk for cigarette escalation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The pulvinar, the largest thalamus nucleus, has rich anatomical connections with several different cortical and subcortical regions suggesting its important involvement in high-level cognitive and emotional functions. Unfortunately, pulvinar dysfunction in psychiatric disorders particularly major depression disorder has not been thoroughly examined to date. In this study we explored the alterations in the baseline regional and network activities of the pulvinar in MDD by applying spectral analysis of resting-state oscillatory activity, functional connectivity and directed (effective) connectivity on resting-state fMRI data acquired from 20 healthy controls and 19 participants with MDD. Furthermore, we tested how pharmacological treatment with duloxetine can modulate the measured local and network variables in ten participants who completed treatment. Our results revealed a frequency-band dependent modulation of power spectrum characteristics of pulvinar regional oscillatory activity. At the network level, we found MDD is associated with aberrant causal interactions between pulvinar and several systems including default-mode and posterior insular networks. It was also shown that duloxetine treatment can correct or overcompensate the pathologic network behavior of the pulvinar. In conclusion, we suggest that pulvinar regional baseline oscillatory activity and its resting-state network dynamics are compromised in MDD and can be modulated therapeutically by pharmacological treatment., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

We present neuroimaging markers of the remitted state of major depressive disorder (rMDD) during facial emotion perception in 84 individuals during fMRI. Participants comprised 47 individuals (aged 18-23) diagnosed with rMDD and 37 healthy controls (HCs). Participants classified emotional faces or animals (control condition) in the Facial Emotion Perception Test (FEPT) during fMRI. Behavioural performance on the FEPT did not differ significantly between groups. During fMRI, both groups demonstrated significant blood oxygen level-dependent (BOLD) activity in bilateral inferior frontal gyri for the faces minus animals (F-A) contrast. The rMDD group additionally showed BOLD activity during F-A in numerous regions, including the bilateral paracingulate gyri, middle temporal gyri and right amygdala. The rMDD group exhibited significantly greater activity than the HC group in regions including the bilateral middle temporal gyri and left superior frontal gyrus. Although the rMDD group did not manifest the behavioural performance deficits on facial emotion recognition tasks that have been observed in actively depressed individuals, the rMDD group nevertheless showed increased BOLD activity compared with never-depressed controls during F-A in multiple posterior brain regions, suggesting that persistent effects of illness or possible trait vulnerabilities may distinguish individuals with rMDD from never-depressed controls., (© The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)

An advantage of separation platforms based on deterministic micro- and nano-fabrications, relative to traditional systems based on packed beds of particles, is the exquisite control of all morphological parameters. For example, with planar platforms based on lithographically-prepared pillar arrays, the size, shape, height, geometric arrangement, and inter pillar gaps can be independently adjusted. Since the inter pillar gap is expected to be important in determining resistance to mass transfer in the mobile phase as well as the flow rate, which influences the mass transfer effect and axial diffusion, we herein study the effect of reducing inter pillar gaps on capillary action-based flow and band dispersion. Atomic layer deposition is used to narrow the gap between the pillars for photo-lithographically defined pillar arrays. The plate height of gap-adjusted arrays is modeled based on predicted and observed flow rates. A reduction in the flow rate with smaller gaps hinders the efficiency in the modeled case and is correlated with actual separations. A conclusion is drawn that simultaneously reducing both the gap and the pillar diameter is the best approach in terms of improving the chromatographic efficiency.

Anhedonia, the diminished anticipation and pursuit of reward, is a core symptom of major depressive disorder (MDD). Trait behavioral activation (BA), as a proxy for anhedonia, and behavioral inhibition (BI) may moderate the relationship between MDD and reward-seeking. The present studies probed for reward learning deficits, potentially due to aberrant BA and/or BI, in active or remitted MDD individuals compared to healthy controls (HC). Active MDD (Study 1) and remitted MDD (Study 2) participants completed the modified monetary incentive delay task (mMIDT), a behavioral reward-seeking task whose response window parameters were individually titrated to theoretically elicit equivalent accuracy between groups. Participants completed the BI Scale and BA Reward-Responsiveness and Drive Scales. Despite individual titration, active MDD participants won significantly less money than HCs. Higher Reward-Responsiveness scores predicted more won; Drive and BI were not predictive. Remitted MDD participants' performance did not differ from controls', and trait BA and BI measures did not predict r-MDD performance. These results suggest that diminished reward-responsiveness may contribute to decreased motivation and reward pursuit during active MDD, but that reward learning is intact in remission. Understanding individual reward processing deficits in MDD may inform personalized intervention addressing anhedonia and motivation deficits in select MDD patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Studies have demonstrated an association between major depressive disorder (MDD) symptoms and fall risk in older adults, which may be at least partially mediated by executive functioning skills. There have also been observations of increased gait variability associated with fall risk and disease. This preliminary study first sought to understand whether gait variability in the context of dual task cost differs among older adults with MDD, relative to those with no history of psychiatric illness, and second, to identify relationships between gait variability measures and cognitive functioning in the context of MDD., Methods: We recruited 15 older adults with MDD and 17 non-depressed (ND) community-dwelling older adults. All participants had impaired balance based on unipedal stance time. Assessments included neuropsychological measures and measures of gait variability using an instrumented gait mat (GAITRite© ) in the context of dual task relative to single task performance (i.e., dual task cost)., Results: The groups did not differ on any gait variability parameters. The MDD group demonstrated poorer performance in the psychomotor speed domain, relative to the ND group, but cognitive functioning between the groups in other domains was equivalent. In MDD, increased variability in stride time, stride velocity, and swing time during dual-tasking were associated with poorer executive functioning and visual memory. In ND, no significant relationships between gait variables and cognitive performance were observed., Conclusions: Findings suggest that unique cognitive mechanisms underlie mobility problems associated with fall risk in late-life depression., (Copyright © 2015 John Wiley & Sons, Ltd.)

Introduction: As prevalence of marijuana use increases, it is important that we better understand how factors like gender, cigarette use, and depression are related to marijuana use during adolescence and young adulthood. We examined longitudinal relationships among these variables in adolescents moving into young adulthood who were studied longitudinally for six years., Methods: 1263 individuals were included in the study. Participants were oversampled for ever-smoking a cigarette at baseline, when they were 15-16 years old. Frequency of cigarette smoking and marijuana use, as well as depression symptoms, were assessed at baseline, 6, 15, 24, 60 and 72 months., Results: Cigarette use frequency and depression symptoms were associated with frequency of marijuana use (p-values<.001), particularly in adolescence, but there were important gender differences in these relationships. Specifically, symptoms of depression were related to marijuana use frequency among males (p<.001), but not females (p=.62). In addition, frequency of marijuana use was associated with increased cigarette use frequency, especially among males who had higher symptoms of depression (p<.001). However, this effect was not seen among females. Exploratory analyses suggested that relationships between frequency of use and depression are specific to marijuana, not cigarettes., Conclusions: Marijuana use is strongly related to depression symptoms and cigarette use frequency in males, indicating that in males these detrimental factors converge, whereas in females they do not. Gender differences in the factors related to marijuana use may mean that there are different risks for and consequences from use and have implications for prevention and intervention efforts., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Co-occurring cannabis and tobacco use has become increasingly prevalent among young adults, but it is not clear how tobacco use may alter the neurocognitive profile typically observed among cannabis users. Although there is substantial evidence citing cannabis and tobacco's individual effect on episodic memory and related brain structures, few studies have examined the effect of combined cannabis and tobacco use on memory., Method: This investigation examined relationships between amount of past year cannabis and tobacco use on 4 different indices of episodic memory among a sample of young adults who identified cannabis as their drug of choice., Results: Results indicated that more cannabis use was linked with poorer initial acquisition, total learning, and delayed recall on the Hopkins Verbal Learning Test-Revised, but only among cannabis users who sporadically smoked cigarettes in the past year. Conversely, the amount of past year cannabis use was not associated with episodic memory performance among individuals who more consistently smoked cigarettes in the past year. These differences could not be explained by several relevant potential confounds., Conclusions: These findings provide important insight into a potential mechanism (i.e., attenuation of cognitive decrements) that might reinforce use of both substances and hamper cessation attempts among cannabis users who also smoke cigarettes. Ongoing and future research will help to better understand how co-use of cannabis and tobacco affects memory during acute intoxication and abstinence and the stability of these associations over time., ((c) 2015 APA, all rights reserved).)

Background: Marijuana use is increasingly widespread among adolescents and young adults; however, few studies have examined longitudinal trajectories of marijuana use during this important developmental period. As such, we examined adolescent trajectories of marijuana use and the psychosocial factors that may differentiate individuals who escalate their marijuana use over adolescence and young adulthood from those who do not., Methods: Participants were 1204 9th and 10th graders at baseline who were over-sampled for cigarette use and were followed over 6-years, as part of an extensive longitudinal study, the Social and Emotional Contexts of Adolescent Smoking Patterns (SECASP) study. Growth Mixture Modeling (GMM) was used to model trajectories of marijuana use and Mixed Effects Regression analyses were used to examine psychosocial correlates of marijuana use escalation over time., Results: Our results revealed three trajectories of non-escalating users (low users, medium users, and high users) and one escalating user trajectory. We found that relative to Non-escalators the Escalators had higher cigarette smoking (p<.0001), novelty-seeking (p=.02), aggressive and anti-social behavior (p<.007), and problem behavior related to peer context (p=.04). Moreover, there were important time and Group by Time interactions in some of these relationships. On the other hand, parental control and depression did not differ between escalators and low and medium non-escalating users., Conclusions: Cigarette smoking, novelty-seeking, aggressive and anti-social behavior, and peer influence are related to 'escalating' marijuana use throughout adolescence and young adulthood., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Previous research has demonstrated that chronic cigarette smoking and major depressive disorder (MDD) are each associated with cognitive decrements. Further, these conditions co-occur commonly, though mechanisms in the comorbid condition are poorly understood. There may be distinct, additive, or overlapping factors underlying comorbid cigarette smoking and MDD. The present study investigated the impact of smoking and MDD on executive function and emotion processing., Methods: Participants (N=198) were grouped by diagnostic category (MDD and healthy controls, HC) and smoking status (ever-smokers, ES and never-smokers, NS). Participants completed the Facial Emotion Perception Test (FEPT), a measure of emotional processing, and the parametric Go/No-go task (PGNG), a measure of executive function., Results: FEPT performance was analyzed using ANCOVA with accuracy and reaction time as separate dependent variables. Repeated measures MANCOVA was conducted for PGNG with performance measure and task level as dependent variables. Analyses for each task included diagnostic and smoking group as independent variables, and gender was controlled for. Results for FEPT reveal that lower overall accuracy was found for ES relative to NS, though MDD did not differ from HC. Post-hoc analyses revealed that ES were poorer at identifying happy and sad, but not fearful or angry, faces. For PGNG, poorer performance was observed in MDD relative to HC in response time to Go targets, but there were no differences for ES and NS. Interaction of diagnosis and smoking group was not observed for performance on either task., Conclusions: The results of this study provide preliminary evidence for distinctive cognitive decrements in smokers and individuals with depression., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: Earlier initiation of cannabis use is associated with poorer neuropsychological functioning across several domains. Given well-documented sex differences in neuromaturation during adolescence, initiation of cannabis use during this time may affect neuropsychological functioning differently for males and females., Method: In the current study, we examined sex differences in the relationship between age of initiated cannabis use and neuropsychological performance after controlling for amount of lifetime cannabis use in 44 male and 25 female young adult cannabis users., Results: We found that an earlier age of initiated use was related to poorer episodic memory, especially immediate recall, in females, but not in males. On the other hand, we found that, surprisingly, an earlier age of initiated use was associated with better decision making overall. However, exploratory analyses found sex-specific factors associated with decision making and age of initiated use, specifically that attention-deficit/hyperactivity disorder (ADHD) symptoms in females may drive the relationship between an earlier age of initiated use and better decision making. Further, an earlier age of initiated use was associated with less education, a lower IQ, and fewer years of mother's education for females, but more lifetime cannabis use for males., Conclusions: Taken together, our findings suggest there are sex differences in the associations between age of initiated cannabis use and neuropsychological functioning. The current study provides preliminary evidence that males and females may have different neuropsychological vulnerabilities that place them at risk for initiating cannabis use and continued cannabis use, highlighting the importance of examining the impact of cannabis on neuropsychological functioning separately for males and females.

Objective: Functional connectivity MRI (fcMRI) studies of individuals currently diagnosed with major depressive disorder (MDD) document hyperconnectivities within the default mode network (DMN) and between the DMN and salience networks (SN) with regions of the cognitive control network (CCN). Studies of individuals in the remitted state are needed to address whether effects derive from trait, and not state or chronic burden features of MDD., Method: fcMRI data from two 3.0 Tesla GE scanners were collected from 30 unmedicated (47% medication naïve) youth (aged 18-23, modal depressive episodes = 1, mean age of onset = 16.2, SD = 2.6) with remitted MDD (rMDD; modal years well = 4) and compared with data from 23 healthy controls (HCs) using four bilateral seeds in the DMN and SN (posterior cingulate cortex (PCC), subgenual anterior cingulate (sgACC), and amygdala), followed by voxel-based comparisons of the whole brain., Results: Compared to HCs, rMDD youth exhibited hyperconnectivities from both PCC and sgACC seeds with lateral, parietal, and frontal regions of the CCN, extending to the dorsal medial wall. A factor analysis reduced extracted data and a PCC factor was inversely correlated with rumination among rMDD youth. Two factors from the sgACC hyperconnectivity clusters were related to performance in cognitive control on a Go/NoGo task, one positively and one inversely., Conclusions: Findings document hyperconnectivities of the DMN and SN with the CCN (BA 8/10), which were related to rumination and sustained attention. Given these cognitive markers are known predictors of response and relapse, hyperconnectivities may increase relapse risk or represent compensatory mechanisms.

The practice of waterpipe smoking (hookah) has rapidly increased in popularity among young adults yet burgeoning research suggests that its use is associated with nicotine dependence and other negative smoking-related health consequences. Moreover, descriptive studies indicate that consumers may hold the belief that hookah smoking is safer than smoking cigarettes. The current study extended previous work by conducting a comprehensive assessment of patterns and contexts of hookah use, psychological correlates of use, co-occurring substance use as well as social norms and health perceptions surrounding the practice. Participants were 143 ethnically diverse undergraduate students at a large urban US university. Approximately half of the sample (48%) reported life-time use of hookah and 22% reported use within the past 30days. Relative to cigarette smoking, hookah smoking was associated with less perceived harm and addiction potential and higher social approval. Participants who reported life-time hookah use, as compared to those who did not, perceived less associated harm, had a greater number of friends who had tried and approved of hookah, were more likely to use cigarettes, marijuana, and alcohol and in higher frequencies and quantities and were at higher risk for problem tobacco and alcohol use. Among participants who were not current smokers, those with hookah experience were more likely to endorse intent to try a cigarette soon. Hookah users did not differ from non-users on measures of trait anxiety, depression and impulsivity though they were more likely to drink alcohol for coping, social and enhancement purposes than non-users. Implications are discussed for public health initiatives to educate young adults about the potential consequences of hookah smoking., (© 2013 Elsevier Ltd. All rights reserved.)

Accumulating evidence suggests neuropsychological deficits from cannabis use, with a burgeoning area of preclinical research indicating possible sex-differences. However, few studies have examined how cannabis use may differentially impact neurocognition in male and female cannabis users. As such, we examined potential sex-differences in associations between amount of cannabis use (across several time frames) and neurocognitive performance among young adult regular cannabis users. Consistent with previous studies, more cannabis use was generally associated with poorer episodic memory and decision-making, but not other measures of inhibitory control. However, patterns of results suggested sex-specific dissociations. In particular, more cannabis use was more consistently associated with poorer episodic memory performance in females than males. Conversely, more cannabis use was associated with poorer decision-making performance for males, but not females. These results provide further evidence for residual cannabis-associated neurocognitive deficits and suggest the importance of examining the impact of cannabis on neurocognition separately for males and females.

Decades of research have examined the effects of cannabis on neurocognition. Recent advances in this field provide us with a better understanding of how cannabis use influences neurocognition both acutely (during intoxication) and non-acutely (after acute effects subside). Evidence of problems with episodic memory is one of the most consistent findings reported; however, several other neurocognitive domains appear to be adversely affected by cannabis use under various conditions. There is significant variability in findings across studies, thus a discussion of potential moderators is increasingly relevant. The purpose of this review was to 1) provide an update on research of cannabis' acute and non-acute effects on neurocognition, with a focus on findings since 2007 and 2) suggest and discuss how neurodevelopmental issues and sex differences may influence cannabis effects on neurocognition. Finally we discuss how future investigations may lead to better understanding of the complex interplay among cannabis, stages of neurodevelopment, and sex on neurocognitive functioning.

A method for hyphenating surface enhanced Raman scattering (SERS) and thin-layer chromatography (TLC) is presented that employs silver-polymer nanocomposites as an interface. Through the process of conformal blotting, analytes are transferred from TLC plates to nanocomposite films before being imaged via SERS. A procedure leading to maximum blotting efficiency was established by investigating various parameters such as time, pressure, and type and amount of blotting solvent. Additionally, limits of detection were established for test analytes malachite green isothiocyanate, 4-aminothiophenol, and Rhodamine 6G (Rh6G) ranging from 10(-7) to 10(-6) M. Band broadening due to blotting was minimal (∼10%) as examined by comparing the spatial extent of TLC-spotted Rh6G via fluorescence and then the SERS-based spot size on the nanocomposite after the blotting process. Finally, a separation of the test analytes was carried out on a TLC plate followed by blotting and the acquisition of distance × wavenumber × intensity three-dimensional TLC-SERS plots.

Cannabis use is associated with risky sexual behavior (RSB) and sex-related negative health consequences. This investigation examined the role of inhibitory control and episodic memory in predicting RSB and sex-related negative consequences among current cannabis users. Findings indicated that the relationships among cannabis, neurocognition, and sexual-risk varied according to the dimension of neurocognition and the parameter of RSB in question. Specifically, more risk-taking was associated with more RSB. Furthermore, amount of recent cannabis use was associated with more RSB and sex-related negative consequences, but only among those with worse performances on a measure of decision-making and of risk-taking. Contrary to hypotheses, worse episodic memory also significantly predicted higher overall sexual-risk and decreased safe-sex practices. Results indicate that worse neurocognitive performance in the areas of risk-taking, decision-making, and episodic memory may influence the degree to which cannabis users engage in RSB and experience negative health consequences as a result. (JINS, 2012, 18, 1-7).

Rationale: Alcohol dependence is associated with high rates of recidivism. Stress has been shown to increase alcohol craving in alcohol-dependent individuals, but the association between stress-induced craving and alcoholism treatment outcome is not well understood., Objective: The aim of the present study was to examine the relationship between strength of stress-induced alcohol craving in the human laboratory and subsequent drinking in a cohort of treatment-seeking, alcohol-dependent adults., Materials and Methods: This is a prospective study assessing stress-induced craving in the lab and subsequent treatment outcomes in alcohol-dependent subjects enrolled in a 12-week outpatient study. Stress was induced using a previously developed, individualized, audio recorded stress script and validated with objective (salivary cortisol) and subjective measures of distress. In vivo craving for alcohol was measured pre- and post-challenge using VAS., Results: Subjects were 28 (16 male, 12 female) alcohol-dependent outpatients. Greater stress-induced craving was associated with a blunted salivary cortisol response, significantly shorter time to alcohol relapse, higher mean drinks per week, fewer percent days abstinent, and lower rates of complete abstinence over the study duration (all p's < 0.05). Conversely, no demographic or baseline variables were significant predictors of any outcome variable., Conclusions: These results suggest that greater stress-related increases in alcohol craving are associated with poorer alcohol treatment outcomes. The findings support the use of stress-induced craving as a predictor of alcohol relapse propensity. Furthermore, treatments that address high stress levels and the associated high levels of alcohol craving are likely to improve treatment outcomes in alcohol dependence.