Relationships Between Prenatal Cocaine Exposure, Cannabis-Use Onset and Emotional and Related Characteristics in Young/Emerging Adults.

Background: Exposure to substances in utero may have significant early-life consequences. Less is known about the effects in emerging adulthood, particularly regarding patterns of substance use and related characteristics.Objectives: In this study, we recruited emerging adults, followed since birth, who had been prenatally exposed, or not, to cocaine. Individuals reported on their cannabis, alcohol, and tobacco use, and measures of impulsivity, anhedonia, emotional regulation, and mental health were obtained. Comparisons were made between emerging adults with prenatal cocaine exposure and those without. Correlations were performed between psychological measures and substance use, and regression analyses were conducted to determine potential pathways by which such measures may relate to prenatal exposure or substance use.Results: Individuals with prenatal cocaine exposure (vs. those without) used cannabis at younger ages, reported greater cannabis-use severity, and demonstrated higher impulsivity, state anxiety, and alexithymia. Earlier age of onset of cannabis use was associated with higher impulsivity, state anxiety, alexithymia, and social and physical anhedonia. Cannabis-use age-of-onset mediated the relationship between prenatal cocaine-exposure status and state anxiety and between prenatal cocaine-exposure status and cannabis-use severity in emerging adulthood but not relationships between prenatal cocaine-exposure status and impulsivity or alexithymia in emerging adulthood. Findings suggest that adults with prenatal cocaine exposure may use cannabis at younger ages, which may relate to increased anxiety and more severe use.Conclusions: These findings suggest both mechanisms and possible intervention targets to improve mental health in emerging adults with prenatal cocaine exposure.

Alexithymia, Emotion-Regulation Strategies, and Traumatic Experiences in Prenatally Cocaine-Exposed Young Adults.

BACKGROUND AND OBJECTIVES: Exposure to early-life trauma may lead to maladaptive characteristics such as alexithymia, and thus to poorer emotional regulation. This relationship may also be influenced by exposure to substances prenatally. We hypothesized that increased alexithymia would be seen in those with prenatal cocaine exposure (PCE). Additionally, we hypothesized that early-life trauma would be associated with alexithymia, and that alexithymia would be associated with poor emotional reappraisal and emotional suppression. METHODS: A moderated mediation model was developed to examine whether the hypothesized indirect relationship between trauma and emotional reappraisal through alexithymia was different in young adults with and without PCE (Total N = 57). Thirty-seven young adults with PCE and 20 with no such exposure, all of whom were members of a longitudinal cohort, were recruited for the study, and data concerning childhood trauma, alexithymia, and emotional regulation were collected. Intercorrelations were performed between the scores on each measure and moderated mediation models were constructed separately with emotional neglect or emotional abuse as the independent variable and emotional reappraisal or emotional suppression as the dependent variable. RESULTS: PCE status was associated with alexithymia, and alexithymia mediated the relationship between emotional neglect and emotional reappraisal in individuals with PCE but not those without. DISCUSSION AND CONCLUSIONS: The data suggest that alexithymia is a mechanism underlying poor use of emotional reappraisal in PCE individuals. SCIENTIFIC SIGNIFICANCE: Individuals with early-life trauma and substance exposure may represent a vulnerable population, and alexithymia may play a key role in the development of emotional regulation skills in this population. (Am J Addict 2020;29:492-499).

Gray-matter relationships to diagnostic and transdiagnostic features of drug and behavioral addictions.

Alterations in neural structure have been reported in both cocaine-use disorder and gambling disorder, separately, suggesting similarities across addiction diagnoses. Individual variation in neural structure has also been associated with impulsivity, a dimensional construct implicated in addictions. This study combines categorical (diagnosis-based) and dimensional (transdiagnostic) approaches to identify neural structural alterations linked to addiction subtypes and trait impulsivity, respectively, across individuals with gambling disorder (n = 35), individuals with cocaine-use disorder (n = 37) and healthy comparison individuals (n = 37). High-resolution T1-weighted data were analyzed using modulated voxel-based morphometry (VBM). Statistical analyses were conducted using whole-brain general-linear models, corrected for family-wise error (pFWE < .05). Categorical analyses indicated a main effect of diagnostic group on prefrontal (dorsal anterior cingulate and ventromedial prefrontal cortex) gray matter volumes (GMVs), involving decreased GMVs among cocaine-use disorder participants only. Dimensional analyses indicated a negative association between trait impulsivity and cortical (insula) and subcortical (amygdala and hippocampus) GMVs across all participants. Conjunction analysis indicated little anatomical overlap between regions identified as differentiating diagnostic groups and regions covarying with impulsivity. These data provide first evidence of neural structural differences between gambling disorder and an illicit substance-use disorder. They further indicate dissociable effects of diagnostic groupings and trait impulsivity on neural structure among individuals with behavioral and drug addictions. Study findings highlight the importance of considering both categorical and dimensional (e.g. Research Domain Criteria; RDoC) analysis approaches within the context of addictions research.

Positive and negative affect in cocaine use disorder treatment: Change across time and relevance to treatment outcome.

BACKGROUND: Cognitive-behavior therapy (CBT) for substance use disorder is empirically supported, and may be associated with change in affect over time. OBJECTIVES: Understanding the role of affect in cocaine use disorder could help to improve CBT outcomes. METHODS: This secondary analysis included 140 adults with cocaine use disorder, 57.9% female, drawn from two randomized controlled studies of web-based cognitive-behavior therapy who completed the Positive and Negative Affect Scale (PANAS) before and during treatment. RESULTS: In mixed-effects regression models, baseline negative affect (NA) scores were not associated with self-reported cocaine use during treatment, but baseline PA scores were associated with less frequent cocaine use (ß = -0.04, p = .02). During treatment, NA scores reduced over time in CBT and treatment as usual (ß = -0.27, p < .01), although PA scores did not change. Higher weekly NA scores were associated with weekly cocaine use (ß = .02, SE = .01, t(746.15) = 2.37, p = .02), although weekly PANAS PA scores were not associated with weekly cocaine use. DISCUSSION AND CONCLUSIONS: Results indicated that individuals with higher baseline PA were more likely to abstain from cocaine use during treatment, even when controlling for baseline cocaine use frequency. Although baseline NA was not associated with cocaine use, NA during treatment was associated with greater cocaine use. SCIENTIFIC SIGNIFICANCE: PA at baseline and NA during treatment were associated with cocaine use. If findings are replicated, treatment developers may wish to include treatment interventions to boost early PA and reduce NA throughout treatment. (Am J Addict 2018;XX:1-8).

Substance-use initiation moderates the effect of stress on white-matter microstructure in adolescents.

BACKGROUND: While childhood stress may contribute risk to substance-use initiation and differences in brain white-matter development, understanding of the potential impact of substance-use initiation on the relationship between experienced stress and white-matter microstructure remains limited. OBJECTIVES: This study examined whether substance-use initiation moderated the effect of perceived stress on white-matter differences using measures of primary white-matter fiber anisotropy. METHODS: Forty adolescents (age 14.75 ± .87 years) were assessed on the Perceived Stress Scale, and 50% were determined to have presence of substance-use initiation. White-matter microstructure was examined using primary-fiber orientations anisotropy, which may reflect white-matter integrity, modeled separately from other fiber orientations in the same voxels. Analyses were conducted on regions of interest previously associated with childhood stress and substance use. RESULTS: Lower perceived stress and presence of substance-use initiation were related to greater right cingulum primary-fiber measures. Substance-use-initiation status moderated the association between perceived stress and right cingulum primary-fiber measures, such that higher perceived stress was associated with lower right cingulum primary-fiber anisotropy in adolescents without substance-use initiation, but not in those with substance-use initiation. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Findings in primary-fiber anisotropy suggest differences in right cingulum white-matter integrity is associated with substance-use initiation in higher-stress adolescents. This reflects a possible pre-existing risk factor, an impact of early substance use, or a combination thereof. Examination of potential markers associated with substance-use initiation in white-matter microstructure among stress-exposed youth warrant additional investigation as such biomarkers may inform efforts relating to tailored interventions. (Am J Addict 2018;27:217-224).

Subscales of alexithymia show unique pathways through reappraisal and suppression to anxiety, depression and stress.

The goal of this work was to explore associations of constituent factors of alexithymia on mental health and potential mediating effects of emotion regulation strategies, specifically suppression and reappraisal. Data were collected through the crowd-sourcing platform Amazon Mechanical Turk (MTURK). Three hundred seventy-seven individuals completed questionnaires related to distress (Depression Anxiety Stress Scales [DASS]), emotion regulation (Emotion Regulation Questionnaire [ERQ]) and Alexithymia (Bermond-Vorst Alexithymia Questionnaire [BVAQ]). Three mediation models were constructed for depression, anxiety and stress, with BVAQ subscales (verbalizing, identifying, emotionalizing, fantasizing, and analyzing) as predictors and ERQ subscales (suppression and reappraisal) as mediators. Results indicated 37.3 % variance in depression, 25.2 % variance in anxiety, and 35.3 % variance in stress was explained by each model. Direct associations revealed emotionalizing and fantasizing were negatively associated with depression, anxiety, and stress, while verbalizing was additionally associated with depression, identifying was additionally associated with anxiety, and all four BVAQ subscales were associated with stress. BVAQ subscales demonstrated negative associations with reappraisal and positive associations with suppression that mediated anxiety and depression. However, suppression did not mediate relationships between BVAQ subscales with stress. Findings support the importance of examining multiple factors of alexithymia and associations with emotion regulation strategies and distress.

Sensitivity, specificity, and discordance with self-report of nail sample testing for alcohol and cannabis.

BACKGROUND: Nails accumulate the alcohol metabolite, ethyl glucuronide (ETG), and the cannabis metabolite, carboxy- delta-9-THC over 3-6 months. Few studies have examined nail toxicology testing's sensitivity and specificity and the agreement between nail testing and self-reported alcohol and marijuana use. METHODS: In an ongoing clinical trial, 1101 veterans completed initial telephone questionnaires and were then asked to mail nail clippings for substance use analysis. We examined sensitivity and specificity of ETG and carboxy- delta-9-THC in nails compared to self-report of alcohol use patterns (the AUDIT-C) and substance-related harms (alcohol and THC subscales of the ASSIST). We then examined factors associated with discordance between nails and self-report. RESULTS: Almost two-thirds (707/1101) of respondents mailed in nail clippings. Those with returned nails were disproportionately married, white race, older, and less depressed. At a threshold of 8pg/mg, sensitivity was only.50 to detect risky alcohol use and.49 to detect alcohol-related issues. Sensitivity for marijuana issues was only.61. Specificity was greater than.77 for all measures. Factors associated with positive nails/negative self-report (i.e. false positives) for risky alcohol use on the Audit-C included more pain and being unmarried; false positive nails for alcohol-related issues on the ASSIST were associated with being unmarried and non-Hispanic ethnicity. False positive nails for THC-related issues on the ASSIST were associated with being African American, Hispanic, and having had legal issues. CONCLUSIONS: At standard cut-offs, nail measures had low sensitivity and higher specificity. The groups who disproportionately submit positive nails/negative self-report could have substance use patterns not adequately captured by self-report, inaccurate self-report due to social pressures, or distinct drug metabolism.

The process of emotion identification: Considerations for psychiatric disorders.

Emotional regulation is important for mental health and behavioral regulation. A relevant precursor to emotional regulation may involve identification of one's emotions. Here, we propose a model of seven components that may provide a foundation for emotion identification. These factors include baseline mood, monitoring, physiological responses, interoception, past personal experiences regarding emotions/metacognition, context, and labeling. We additionally examine how deficits in different components may contribute to the concept of alexithymia, which is defined by difficulty identifying and describing one's own emotions. Ultimately, we explore how the model may support a relationship between specific psychiatric disorders and alexithymia. The proposed model may help explain emotional identification impairment in multiple psychiatric disorders and guide future research and treatment development efforts.

A Mini-Review of Relationships Between Cannabis Use and Neural Foundations of Reward Processing, Inhibitory Control and Working Memory.

Cannabis is commonly used, and use may be increasing in the setting of increasing legalization and social acceptance. The scope of the effects of cannabis products, including varieties with higher or lower levels of Δ9-tetrahydrocannabinol (THC) or cannabidiol (CBD), on domains related to addictive behavior deserves attention, particularly as legalization continues. Cannabis use may impact neural underpinnings of cognitive functions linked to propensities to engage in addictive behaviors. Here we consider these neurocognitive processes within the framework of the dual-process model of addictions. In this mini-review, we describe data on the relationships between two main constituents of cannabis (THC and CBD) and neural correlates of reward processing, inhibitory control and working memory.

Longitudinal changes in network engagement during cognitive control in cocaine use disorder.

BACKGROUND: Cocaine use disorder (CUD) is characterized by poor cognitive control and has limited empirically supported treatment options. Furthermore, an understanding of brain mechanisms underlying CUD is at a relatively early stage. Thus, this study aimed to investigate longitudinal alterations in functional neural networks associated with cognitive control in cocaine use disorder (CUD). METHODS: Secondary analysis was performed on data from 44 individuals who participated in three randomized clinical trials for CUD and completed an fMRI Stroop task both at baseline and post-treatment. Independent component analysis (ICA) was performed to assess changes in functional network engagement and investigate associations with cocaine-use behaviors. Mixed linear models were performed to test for longitudinal effects on network engagement and relationships with baseline patterns of cocaine use (i.e., past-month frequency and lifetime years of use) and periods of abstinence/use between scans (i.e., percent negative urine toxicology and maximum days of contiguous abstinence). RESULTS: Six functional networks were identified as being related to cognitive control and/or exhibiting changes in engagement following treatment. Results indicated that engagement of amygdala-striatal, middle frontal and right-frontoparietal networks were reduced over time in CUD. Less change in the amygdala-striatal network was associated with greater lifetime years of cocaine use. Additional analyses revealed that negative toxicology results and achievement of continuous abstinence were associated with greater engagement of the right-frontoparietal network. CONCLUSIONS: Neural systems that underlie cognitive control may change over time in individuals with CUD. A longer history of cocaine-use may hinder changes in network activity, potentially impeding recovery.

Daily cannabis use in adolescents who smoke tobacco is associated with altered late-stage feedback processing: A high-density electrical mapping study.

Impairments in feedback processing, often associated with risk-taking behavior, may have implications for development of substance abuse in adolescents. The most commonly used substances by adolescents include tobacco and cannabis, with some individuals using both substances, potentially heightening risk. Our objective was to examine feedback processing and impulsivity in adolescents who smoke cigarettes and use cannabis daily (N = 21), comparing them with adolescents who smoke cigarettes daily and use cannabis occasionally (N = 18) and non-smoking (N = 27) adolescents. To do this, the Balloon Analog Risk Task (BART) with concurrent EEG was used to measure risk-related feedback processing, and impulsivity was measured using the Barratt's impulsiveness scale (BIS-11). It was found that adolescent daily tobacco/cannabis smoking was associated with higher BIS-11 scores, shortened feedback-related-negativity (FRN) latencies and reduced P300 amplitudes. In addition, FRN latencies during win conditions were inversely associated with tobacco-use severity, indicated by scores on the Fagerstrom Test for Nicotine Dependence (FTND), and with BIS-11 scores. Adolescents with concurrent tobacco and cannabis use show altered feedback processing and higher impulsivity. Future work should disentangle whether the effect reflects risk, consequences of use or both.

Alexithymia and pain experience among patients using methadone-maintenance therapy.

BACKGROUND: Alexithymia, difficulty identifying and describing one's emotions coupled with a tendency to externalize, is a potentially important yet understudied treatment target for patients with opioid use disorder. The aim of this study was to examine the role of alexithymia in pain experience among individuals with opioid use disorder. METHODS: One-hundred-and-sixty-four patients receiving methadone maintenance treatment completed a battery of self-report measures related to alexithymia, drug use, and pain experiences. Comparisons were performed on the full sample between those with or without clinically significant levels of alexithymia. For a subsample reporting pain (n = 138), intercorrelations were performed to test whether drug use history, pain catastrophizing, pain acceptance, and alexithymia were related to pain severity and pain interference. Regression analyses were performed to test for serial mediation of pain catastrophizing and pain acceptance on the relationship between alexithymia and pain interference in this subsample. RESULTS: Individuals with alexithymia showed increased pain catastrophizing and interference, and intercorrelations indicated that increased alexithymia was associated with increased pain interference, more pain catastrophizing, and reduced pain acceptance. A serial regression model among a subset of patients with pain indicated that pain catastrophizing and pain acceptance mediated the effect of alexithymia on pain interference. CONCLUSIONS: These findings suggest that alexithymia, as well as both pain catastrophizing and pain acceptance, contribute to interference associated with pain and are potentially important intervention targets among methadone-treated patients with pain.

Mood Disorders in High-Functioning Autism: The Importance of Alexithymia and Emotional Regulation.

Individuals with autism spectrum disorder (ASD) often have co-morbid anxiety and depression. Alexithymia and emotion regulation difficulties are commonly seen in individuals with ASD and in mood disorders. We hypothesized that alexithymia and emotional regulation would mediate the relationship between autistic features and anxiety/depression symptom severity. We collected data about emotional regulation, alexithymia, autistic symptoms and depression/anxiety in a sample of 64 young adults with ASD. We constructed two serial multiple mediator models, using autistic features as the independent variable and anxiety/depression symptoms as outcome variables. The serial relationship between alexithymia and emotional regulation mediated associations between autistic features and depression and anxiety, separately. The findings suggest that targeting alexithymia may benefit therapies designed to alleviate mood disorders in ASD.

Prenatal drug exposure from infancy through emerging adulthood: Results from neuroimaging.

Prenatal drug exposure may have important repercussions across the lifespan for cognition and behavior. While alcohol is a recognized teratogen, the influences of other substances may also be substantial. The neural underpinnings of the influences of prenatal drug exposure have been examined using longitudinal approaches and multiple imaging techniques. Here we review the existing literature on the neural correlates of prenatal drug exposure. We focused the review on studies that have employed functional neuroimaging and electroencephalography and on substances other than alcohol. We also framed the review through the lens of four developmental life stages (infancy, childhood, adolescence and emerging adulthood). We included papers that have examined any drug use, including tobacco, opiates, cocaine, marijuana, methamphetamines, or polysubstance use. Data suggest that prenatal drug exposure has long-lasting, deleterious influences on cognition and reward processing in infancy and childhood that persist into adolescence and emerging adulthood and may underlie some behavioral tendencies, such as increased externalizing and risk-taking behaviors, seen in these groups.

Oscillatory Dynamics of Feedback Processing in Adolescents with Prenatal Cocaine Exposure.

Prenatal cocaine exposure (PCE) has ramifications for feedback processing. Measuring neural oscillatory dynamics (during electroencephalography) provides insight into the time signatures and neural processes of feedback processing in adolescents with PCE. We measured spectral power in alpha and theta frequency bands while 49 adolescents with PCE and 34 non-drug exposed (NDE) performed a task with win/no-win feedback. Compared to NDE individuals, those with PCE showed reduced alpha power and increased theta power in response to no-win feedback. These findings suggest altered reactivity in PCE adolescents.

Gradient theories of brain activation: A novel application to studying the parental brain.

PURPOSE OF REVIEW: Parental brain research primarily employs general-linear-model-based (GLM-based) analyses to assess blood-oxygenation-level-dependent responses to infant auditory and visual cues, reporting common responses in shared cortical and subcortical structures. However, this approach does not reveal intermixed neural substrates related to different sensory modalities. We consider this notion in studying the parental brain. RECENT FINDINGS: Spatial independent component analysis (sICA) has been used to separate mixed source signals from overlapping functional networks. We explore relative differences between GLM-based analysis and sICA as applied to an fMRI dataset acquired from women while they listened to infant cries or viewed infant sad faces. SUMMARY: There is growing appreciation for the value of moving beyond GLM-based analyses to consider brain functional organization as continuous, distributive, and overlapping gradients of neural substrates related to different sensory modalities. Preliminary findings suggest sICA can be applied to the study of the parental brain.

Feedback processing in adolescents with prenatal cocaine exposure: an electrophysiological investigation.

Impaired cognitive control is a consequence of cocaine exposure. Difficulty with feedback processing may underlie this impairment. We examined neural correlates of feedback processing using event-related potentials (ERPs) in 49 prenatally cocaine-exposed (PCE) and 34 nondrug exposed (NDE) adolescents. Adolescents performed a reward-feedback task with win/no-win feedback in a chance-based task. We investigated amplitude and latency of the feedback-related negativity (FRN) and P300 ERP components and source-based estimates elicited during feedback processing. PCE adolescents had smaller P300 amplitudes for no-win feedback, and source analysis in the P300 time window revealed differences between groups localized to the dorsal anterior cingulate cortex.

Shared microstructural features of behavioral and substance addictions revealed in areas of crossing fibers.

BACKGROUND: Similarities between behavioral and substance addictions exist. However, direct neurobiological comparison between addictive disorders is rare. Determination of disorder-specificity (or lack thereof) of alterations within white-matter microstructures will advance understanding of the pathophysiology of addictions. METHODS: We compared white-matter microstructural features between individuals with gambling disorder (GD; n=38), cocaine-use disorder (CUD; n=38) and healthy comparison (HC; n=38) participants, as assessed using diffusion-weighted magnetic resonance imaging (dMRI). To provide a more precise estimate of diffusion within regions of complex architecture (e.g., cortico-limbic tracts), analyses were conducted using a crossing-fiber model incorporating local-orientation modeling (tbss_x). Anisotropy estimates for primary and secondary fiber orientations were compared using ANOVAs corrected for multiple comparisons across space using threshold-free cluster enhancement (pFWE<.05). RESULTS: A main effect of group on anisotropy of secondary fiber orientations within the left internal capsule, corona radiata, forceps major and posterior thalamic radiation, involving reduced anisotropy among GD and CUD participants in comparison to HC participants. No differences in anisotropy measures were found between GD and CUD individuals. CONCLUSIONS: This is the first study to compare diffusion indices directly between behavioral and substance addictions and the largest dMRI study of GD. Our findings indicate similar white-matter microstructural alterations across addictions that cannot be attributed solely to exposure to drugs or alcohol and thus may be a vulnerability mechanism for addictive disorders.

White-matter crossing-fiber microstructure in adolescents prenatally exposed to cocaine.

BACKGROUND: Prenatal cocaine exposure (PCE) is associated with risk-taking behaviors, including increased initiation of substance use in adolescence. The neurobiological underpinnings of these behaviors in adolescents with PCE are not well understood. The goal of this study was to compare diffusion-weighted imaging data between adolescents with and without PCE using crossing-fiber models, which may provide more comprehensive estimates of white-matter microstructure within regions of multiple (e.g., primary and secondary) fiber orientations. METHODS: Thirty-nine PCE individuals and 17 comparably aged prenatally non-drug-exposed (NDE) youths were recruited from a longitudinal cohort followed since birth. White matter was examined using tensor-derived and crossing-fiber models. Whole-brain investigations were performed, as were analyses on seven white-matter regions, which included the splenium, body and genu of the corpus callosum, bilateral cingulum, and the right and left superior longitudinal fasciculus (SLF). RESULTS: Whole-brain analyses revealed no group differences. However, ROI analyses for anisotropy estimates derived from the crossing-fiber model revealed significant group differences for secondary fibers, with reduced anisotropy among PCE adolescents compared to prenatally non-exposed youth in the right cingulum and the left SLF, and increased anisotropy in the genu. CONCLUSIONS: Our findings suggest that white-matter differences in PCE adolescents are subtle and localized primarily within secondary fiber orientations, perhaps arising from altered white-matter development.