Predicting Acute Changes in Suicidal Ideation and Planning: A Longitudinal Study of Symptom Mediators and the Role of the Menstrual Cycle in Female Psychiatric Outpatients With Suicidality.

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.

Methamphetamine alters nucleus accumbens neural activation to monetary loss in healthy young adults.

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.

Preliminary evidence that individuals with remitted alcohol use disorder and major depressive disorder exhibit enhanced neural responses to reward: An EEG study.

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.

Reduced connectivity of the cognitive control neural network at rest in young adults who had their first drink of alcohol prior to age 18.

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.

Effects of Cannabidiol in Adolescent and Young Adult Depressive and Anxiety Disorders: A Systematic Review of Clinical and Preclinical Research.

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.

Electrocortical measures of win and loss processing are associated with mesocorticolimbic functional connectivity: A combined ERP and rs-fMRI study.

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.

Risk factors for alcohol, marijuana, and cigarette polysubstance use during adolescence and young adulthood: A 7-year longitudinal study of youth at high risk for smoking escalation.

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.

Individual differences in striatal and amygdala response to emotional faces are related to symptom severity in social anxiety disorder.

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.

Effect of Δ9-Tetrahydrocannabinol on frontostriatal resting state functional connectivity and subjective euphoric response in healthy young adults.

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.

Striatal activation to monetary reward is associated with alcohol reward sensitivity.

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.

Neural activation during anticipation of monetary gain or loss does not associate with positive subjective response to alcohol in binge drinkers.

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.

Cannabis users demonstrate enhanced neural reactivity to reward: An event-related potential and time-frequency EEG study.

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.

A Lifespan Model of Interference Resolution and Inhibitory Control: Risk for Depression and Changes with Illness Progression.

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.

Developing Dimensional, Pandiagnostic Inhibitory Control Constructs With Self-Report and Neuropsychological Data.

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.

Anticipation of monetary reward in amygdala, insula, caudate are predictors of pleasure sensitivity to d-Amphetamine administration.

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.

Neural correlates of inhibition and reward are negatively associated.

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.

Multidimensional imaging techniques for prediction of treatment response in major depressive disorder.

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.

Developmental changes in resting-state functional networks among individuals with and without internalizing psychopathologies.

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.

Distress intolerance moderation of neurophysiological markers of response inhibition after induced stress: Relations with cannabis use disorder.

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).

Amygdala-orbitofrontal functional connectivity mediates the relationship between sensation seeking and alcohol use among binge-drinking adults.

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.