Group behavioral activation with and without a smartphone app in intensive outpatient treatment for substance use disorder: A three-arm randomized controlled trial.

INTRODUCTION: Reward deficits negatively impact recovery from substance use disorder (SUD). LETS ACT, a behavioral activation treatment targeting substance-free reward, has demonstrated effectiveness in reducing post treatment substance use. There remains room for modifications to extend recovery gains, and LETS ACT remains largely untested in outpatient treatment. We tested the effect of LETS ACT when delivered alongside intensive outpatient SUD treatment, with and without a smartphone app designed to extend access to treatment content outside of clinician-administered sessions. METHODS: In this three-arm randomized controlled trial (N = 206; 54 % White, 67 % male), all participants received intensive outpatient SUD treatment as usual (TAU) and either LETS ACT (n = 56), smartphone-enhanced LETS ACT (n = 65), or assessments only (n = 61). Substance use days and substance related problems were assessed through 12 months posttreatment. RESULTS: Generalized estimating equations indicated a significant condition*time interaction for substance use days; Days of substance use significantly declined from pretreatment until 1-month for TAU, 3-months for LETS ACT-SE, and 6-months for LETS ACT. Decreases in substance-related problems were maintained across all conditions through 12 months. CONCLUSIONS: Adding LETS ACT to intensive outpatient treatment resulted in significant decreases in substance use through 6 months posttreatment, yet these gains were not sustained through 12 months posttreatment. A smartphone app did not facilitate superior treatment outcomes. Future studies should consider factors impacting treatment efficacy in outpatient settings and the utility of providing more than six sessions of behavioral activation.

Measuring morality: Analyzing the factor structure of the moral foundations questionnaire in veterans.

OBJECTIVES: Moral reasoning is an underexamined and potentially useful area of research relative to the care of moral injury in veterans. However, the most widely used measure of moral reasoning, the moral foundations questionnaire (MFQ), has not been validated in this population. METHODS: Post-9/11 veterans (N = 311) completed questionnaires which included the MFQ. Veterans' scores were compared to the general US population. Confirmatory factor analysis was used to test existing models of the MFQ in the sample. Exploratory factor analysis (EFA) was also used to examine potentially improved model fits. RESULTS: The two leading, preexisting MFQ models were both poor fits for the data. EFA results produced a four-factor model for the veteran sample using 25 of the original 30 items of the MFQ. CONCLUSIONS: Measuring moral reasoning among veterans may be important in understanding the experience of moral injury. However, the most widely used scale (MFQ) performs poorly among a sample of post-9/11 veterans, indicating that veterans may respond differently to the measure than the general US population. Military culture may uniquely influence veterans' moral reasoning, suggesting the need for military specific measures for this construct.

Alpha-tACS effect on inhibitory control and feasibility of administration in community outpatient substance use treatment.

BACKGROUND: Deficits in inhibitory control (IC) and distress tolerance (DT) are associated with substance use disorders (SUD) and post-treatment return to substance use. Transcranial alternating current stimulation (tACS) modulates the neural oscillations that are associated with the cognitive and affective mechanisms contributing to IC and DT. The aims of the current study were to examine the feasibility and acceptability of administering tACS in a community-based SUD treatment setting, and to test the effect of alpha-tACS on IC and DT. METHOD: A double-blind, randomized, active sham-controlled trial of treatment-seeking adults with a SUD (N = 30, Meanage = 43.2 years, 70.0% male). Participants attended two sessions and completed computerized inhibitory control and distress tolerance tasks while receiving tACS targeting the bilateral dorsolateral prefrontal cortex (DLPFC). Participants received sham-tACS and were then randomized to receive sham-, alpha-, or gamma-tACS within 2-3 days. RESULTS: Treatment retention was 87%. Participant self-reported belief of having received tACS and mean side effect intensity ratings did not differ across conditions, with all side effect ratings in the absent to mild range. There was a large (d = 0.83) and significant effect of alpha-tACS on inhibitory control compared to sham-tACS (ß = 1.78, SE = 0.65, 95 % CI: 0.41, 3.14, p<0.01). There were no significant effects of condition on distress tolerance. CONCLUSIONS: To our knowledge, this is the first study of tACS in adults with a SUD. Our findings provide preliminary evidence for recruitment, retention, and administration feasibility of tACS in a community-based substance use treatment program and a beneficial effect of alpha-tACS on inhibitory control.

Triple Network Resting State Connectivity Predicts Distress Tolerance and Is Associated with Cocaine Use.

Distress tolerance (DT), a predictor of substance use treatment retention and post-treatment relapse, is associated with task based neural activation in regions located within the salience (SN), default mode (DMN), and executive control networks (ECN). The impact of network connectivity on DT has yet to be investigated. The aim of the present study was to test within and between network resting-state functional connectivity (rsFC) associations with DT, and the impact of cocaine use on this relationship. Twenty-nine adults reporting regular cocaine use (CU) and 28 matched healthy control individuals (HC), underwent resting-state functional magnetic resonance imaging followed by the completion of two counterbalanced, computerized DT tasks. Dual-regression analysis was used to derive within and between network rsFC of the SN, DMN, and lateralized (left and right) ECN. Cox proportional-hazards survival models were used to test the interactive effect of rsFC and group on DT. The association between cocaine use severity, rsFC, and DT was tested within the CU group. Lower LECN and higher DMN-SN rsFC were associated with DT impairment. Greater amount of cocaine use per using day was associated with greater DMN-SN rsFC. The findings emphasize the role of neural resource allocation within the ECN and between DMN-SN on distress tolerance.

Neural reward response to substance-free activity images in opiate use disorder patients with depressive symptoms.

BACKGROUND: Deficits in the ability to experience reward from natural, substance-free activities and stimuli is a common mechanism contributing to both opiate use disorder and depressive symptoms, and is a target of behavioral-focused treatments for substance use and depression. Although the neural response to monetary, positive affect-eliciting and social images has been investigated, the neural response to images representing substance-free activity engagement remains untested. The current study tested the neural response to anticipation and receipt of substance-free activity engagement images and monetary reward in opiate use disorder patients with elevated depressive symptoms compared to healthy controls. METHODS: Sixteen male opiate use disorder detoxification patients with elevated depressive symptoms (Beck Depression Inventory (BDI-II) ≥ 14) (OUDD Mage = 32.19 years, SD = 8.17 years) and seventeen male healthy controls (BDI-II < 14) (HC: Mage = 26.82 years, SD = 5.29 years) completed the Monetary Incentive Delay (MID) and newly developed Activity Incentive Delay (AID) tasks. Within- and between-group whole-brain contrasts tested activation during anticipation ([reward]-[non-reward]) and receipt ([win]-[non-win]) of substance-free activity image, monetary, and substance-free activity relative to monetary (AID-MID), reward. RESULTS: OUDD demonstrated significantly lower activation in reward regions during anticipation and significantly greater activation during receipt of substance-free activity image reward compared to HC. OUDD demonstrated significantly lower activation during anticipation of substance-free activity reward relative to monetary reward, compared to HC. CONCLUSIONS: The observed reduction in frontostriatal response to reward anticipation of substance-free activity engagement images in OUDD, yet increased neural response to reward receipt, supports theory linking reductions in reward processing with deficits in motivation for substance-free activity engagement.

Why do trauma survivors become depressed? Testing the behavioral model of depression in a nationally representative sample.

Despite accumulated evidence linking trauma exposure to major depressive disorder (MDD), there is limited understanding as to why some trauma survivors subsequently develop MDD. The behavioral model of depression points to a negative reinforcement cycle of trauma-related avoidance and depressed mood, but no study has evaluated this framework in trauma survivors. This study tested the hypothesis that traumatic stress symptom-related interference with daily activities and with relationships and self-medicating traumatic stress symptoms with alcohol and with drugs would predict MDD onset in a nationally representative sample after controlling for established risk factors. Data were drawn from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) using two samples: adults reporting lifetime trauma exposure but no history of MDD at Wave 1 (n = 8301) and a subset of those participants who met criteria for lifetime PTSD prior to Wave 1 (n = 1055). Younger age, female gender, a greater number of different trauma types, traumatic stress-related interference with daily activities, and self-medicating traumatic stress symptoms with alcohol significantly predicted MDD onset in both groups. Findings underscore the role of traumatic stress-related interference and self-medication in the development of MDD.

Brain Mechanisms of Attention Orienting Following Frustration: Associations With Irritability and Age in Youths.

OBJECTIVE: Childhood irritability is a common, impairing problem with changing age-related manifestations that predict long-term adverse outcomes. However, more investigation of overall and age-specific neural correlates is needed. Because youths with irritability exhibit exaggerated responses to frustrating stimuli, the authors used a frustration functional MRI (fMRI) paradigm to examine associations between irritability and neural activation and tested the moderating effect of age. METHOD: The authors studied a transdiagnostic sample of 195 youths with varying levels of irritability (disruptive mood dysregulation disorder, N=52; anxiety disorder, N=42; attention deficit hyperactivity disorder, N=40; and healthy volunteers, N=61). Irritability was measured by parent and child reports on the Affective Reactivity Index. The fMRI paradigm was a cued-attention task differentiating neural activity in response to frustration (rigged feedback) from activity during attention orienting in the trial following frustration. RESULTS: Whole-brain activation analyses revealed associations with irritability during attention orienting following frustration. Irritability was positively associated with frontal-striatal activation, specifically in the dorsolateral prefrontal cortex, inferior frontal gyrus, and caudate. Age moderated the association between irritability and activation in some frontal and posterior regions (the anterior cingulate cortex, medial frontal gyrus, cuneus, precuneus, and superior parietal lobule [F=19.04-28.51, df=1, 189, partial eta squared=0.09-0.13]). Specifically, higher irritability was more strongly related to increased activation in younger youths compared with older youths. CONCLUSIONS: Following frustration, levels of irritability correlated with activity in neural systems mediating attention orienting, top-down regulation of emotions, and motor execution. Although most associations were independent of age, dysfunction in the anterior cingulate cortex and posterior regions was more pronounced in young children with irritability.

Distress tolerance among substance users is associated with functional connectivity between prefrontal regions during a distress tolerance task.

Distress tolerance (DT), defined as the ability to persist in goal directed behavior while experiencing affective distress, is implicated in the development and maintenance of substance use disorders. While theory and evidence indicate that cortico-limbic neural dysfunction may account for deficits in goal directed behavior while experiencing distress, the neurobiological mechanisms of DT have yet to be examined. We modified a computerized DT task for use in functional magnetic resonance imaging (fMRI), the Paced Auditory Serial Addition Task (PASAT-M), and examined the neural correlates and functional connectivity of DT among a cohort of substance users (n = 21; regular cocaine and nicotine users) and healthy controls (n = 25). In response to distress during the PASAT-M, we found greater activation in a priori cortico-limbic network ROIs, namely the right insula, anterior cingulate cortex (ACC), bilateral medial frontal gyrus (MFG), right inferior frontal gyrus (IFG) and right ventromedial prefrontal cortex (vmPFC) significantly predicted higher DT among substance users, but not healthy controls. In addition, greater task-specific functional connectivity during distress between the right MFG and bilateral vmPFC/sgACC was associated with higher DT among substance users, but not healthy controls. The observed positive relationship between DT and neural activation in cortico-limbic structures, as well as functional connectivity between the rMFG and vmPFC/sgACC, is in line with theory and research suggesting the importance of these structures for persisting in goal directed behavior while experiencing affective distress.

Increased intrasubject variability in response time in unaffected preschoolers at familial risk for bipolar disorder.

Increased intrasubject variability in response time (ISVRT) is evident in healthy preschoolers at familial risk for bipolar disorder, suggesting it may be an endophenotype.

Parametric modulation of neural activity during face emotion processing in unaffected youth at familial risk for bipolar disorder.

OBJECTIVES: Both patients with pediatric bipolar disorder (BD) and unaffected youth at familial risk (AR) for the illness show impairments in face emotion labeling. Few studies, however, have examined brain regions engaged in AR youth when processing emotional faces. Moreover, studies have yet to explore neural responsiveness to subtle changes in face emotion in AR youth. METHODS: Sixty-four unrelated youth, including 20 patients with BD, 15 unaffected AR youth, and 29 healthy comparisons (HC), completed functional magnetic resonance imaging. Neutral faces were morphed with angry or happy faces in 25% intervals. In specific phases of the task, youth alternatively made explicit (hostility) or implicit (nose width) ratings of the faces. The slope of blood oxygenated level-dependent activity was calculated across neutral to angry and neutral to happy face stimuli. RESULTS: Behaviorally, both subjects with BD (p ≤ 0.001) and AR youth (p ≤ 0.05) rated faces as less hostile relative to HC. Consistent with this, in response to increasing anger on the face, patients with BD and AR youth showed decreased modulation in the amygdala and inferior frontal gyrus (IFG; BA 46) compared to HC (all p ≤ 0.05). Amygdala dysfunction was present across both implicit and explicit rating conditions, but IFG modulation deficits were specific to the explicit condition. With increasing happiness, AR youth showed aberrant modulation in the IFG, which was also sensitive to task demands (all p ≤ 0.05). CONCLUSIONS: Decreased amygdala and IFG modulation in patients with BD and AR youth may be pathophysiological risk markers for BD, and may underlie the social cognition and face emotion labeling deficits observed in BD and AR youth.