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IMPORTANCE: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. OBJECTIVE: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. EVIDENCE REVIEW: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. FINDINGS: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. CONCLUSIONS AND RELEVANCE: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

Disrupted brain gamma‐aminobutyric acid (GABA)/glutamate homeostasis is a promising target for pharmacological intervention in co‐occurring bipolar disorder (BD) and cannabis use disorder (CUD). Gabapentin is a safe and well‐tolerated medication, FDA‐approved to treat other neurological diseases, that restores GABA/glutamate homeostasis, with treatment studies supporting efficacy in treating CUD, as well as anxiety and sleep disorders that are common to both BD and CUD. The present manuscript represents the primary report of a randomized, double‐blind, placebo‐controlled, crossover (1‐week/condition), multimodal‐MRI (proton‐MR spectroscopy, functional MRI) pilot study of gabapentin (1200 mg/day) in BD + CUD (n = 22). Primary analyses revealed that (1) gabapentin was well tolerated and adherence and retention were high, (2) gabapentin increased dorsal anterior cingulate cortex (dACC) and right basal ganglia (rBG) glutamate levels and (3) gabapentin increased activation to visual cannabis cues in the posterior midcingulate cortex (pMCC, a region involved in response inhibition to rewarding stimuli). Exploratory evaluation of clinical outcomes further found that in participants taking gabapentin versus placebo, (1) elevations of dACC GABA levels were associated with lower manic/mixed and depressive symptoms and (2) elevations of rBG glutamate levels and pMCC activation to cannabis cues were associated with lower cannabis use. Though promising, the findings from this study should be interpreted with caution due to observed randomization order effects on dACC glutamate levels and identification of statistical moderators that differed by randomization order (i.e. cigarette‐smoking status on rBG glutamate levels and pMCC cue activation). Nonetheless, they provide the necessary foundation for a more robustly designed (urn‐randomized, parallel‐group) future study of adjuvant gabapentin for BD + CUD. [ABSTRACT FROM AUTHOR]

The aim of the study was to examine whether Borderline Personality Disorder (BPD) features moderate the relation between dating violence victimization (DVV) experiences and nonsuicidal self-injury (NSSI) in adolescent inpatients. A total of 184 adolescent inpatients completed measures on DVV, BPD features, and NSSI at admission to treatment. Bivariate analyses revealed significant relations between DVV, BPD features, and NSSI. Hierarchical multiple regression analyses demonstrated a moderating effect of BPD features such that in the low BPD features group, more severe DVV was associated with greater NSSI frequency; adolescents in the high BPD group endorsed elevated, though stable, levels of NSSI at all levels of DVV. BPD features differentially affect the relationship between DVV and NSSI. Low BPD adolescents exposed to high DVV appear to self-injure more frequently and at rates similar to high BPD adolescents when faced with more severe DVV, while DVV appears neither necessary nor sufficient to be the cause of NSSI in high BPD adolescents. Our results indicate that DVV may be a particularly important focal point for treating adolescents who self-injure and have been victimized by a dating partner. As such, Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) and Dialectical Behavior Therapy (DBT) may serve as valuable clinical interventions. [ABSTRACT FROM AUTHOR]

The identification of theoretically and empirically supported correlates of suicide ideation is important to improve treatment approaches to suicide. This study sought to examine the association between interpersonal trust (theoretically conceptualized as a distal risk marker) and suicide ideation in adolescence. Specifically, it was hypothesized that interpersonal trust would be negatively associated with suicide ideation via perceived burdensomeness and thwarted belongingness (conceptualized as more proximal risk markers). Data were drawn from a cross-sectional sample of 387 adolescent inpatients between the ages of 12 and 17 years (M = 14.72, SD = 1.49). The sample was 63.6% female, 37.5% Hispanic, 26.9% African American/Black, and 25.8% Caucasian. Adolescents completed a series of self-report measures to assess thwarted belongingness, perceived burdensomeness, interpersonal trust, depressive symptoms, and suicide ideation. A structural equation model was fit to the data, and results demonstrated a significant indirect path from interpersonal trust to suicide ideation via perceived burdensomeness, but not thwarted belongingness. Results suggest that interpersonal trust may be a distal risk marker for suicide ideation and that interventions to increase interpersonal trust may help prevent the development of thwarted belongingness, perceived burdensomeness, and suicide ideation. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorder (AUD) is thought to bias the neurocircuitry underlying reward processing and motivation to preferentially attend to conditioned alcohol cues over natural rewards. The present case-control pilot study evaluated this hypothesis using novel natural reward paradigms., Methods: Twenty-eight participants (AUD, n = 14, light drinkers, n = 14) were recruited-AUD participants reported 44.0% heavy drinking days (%HDD) and 4.67 drinks/day over the preceding 90 days. Functional magnetic resonance imaging (fMRI) data were acquired during the administration of three separate picture-viewing paradigms of alcohol cues, food scenes, and social reward, respectively. Independent samples t-tests were performed to compare groups' fMRI data and exploratory correlation analyses were performed to examine associations with clinical characteristics of AUD., Results: Food scenes elicited abnormally low reward-related activation, within the superior frontal gyrus and caudate bilaterally, among AUD participants. Lower activation to food scenes within the superior frontal gyrus was, in turn, associated with higher levels of past-month %HDD among AUD participants, specifically, along with craving and alcohol dependence severity when examined across the full sample. Contrasting reward types (e.g., alcohol cues vs. food scenes) did not reveal "preferential" activation to differentiate groups., Conclusions: Heavy drinking appears associated with reduced responsivity to natural rewards, specifically food rather than social cues. Neural mechanisms underlying the high prevalence of malnutrition among individuals with AUD may involve some combination of blunted approach-related affect and reduced craving-related motivation to eat when food is present, resulting in limited engagement of cortico-striato-thalamic motor circuitry supporting food acquisition. However, given the preliminary nature of this pilot study, such formulations remain tentative until larger follow-up studies can be conducted. From a potential translational standpoint, the ability of promising therapeutics to demonstrate increased responsivity to natural rewards, specifically nutritive reward may serve as a valuable complementary efficacy indicator for future clinical neuroimaging trials in AUD., (© 2024 Research Society on Alcohol.)

Background: Bipolar disorder (BD) and alcohol use disorder (AUD) often co-occur, with BD + AUD characterized by higher levels of impulsivity relative to either disorder alone. Emotional facets of impulsivity (e.g., "urgency," measured by the UPPS-P), however, remain underexplored in this population and could have distinct associations with clinical correlates., Methods: This cross-sectional study used a two-by-two (BDxAD) factorial design, including groups with BD + AD (n = 28), BD (n = 29), AD (n = 28), and healthy controls (HC) (n = 27), to identify between-group differences among the five subscales of the UPPS-P. Associations of UPPS-P subscales with Barratt Impulsiveness Scale (BIS) total scores and clinical variables of interest were also examined., Results: BD + AD had the highest scores for every UPPS-P subscale but Sensation Seeking, with the Positive and Negative Urgency subscales having the largest main effects for both BD and AD. BIS-11 total scores were most correlated with the urgency subscales of the UPPS-P. Negative Urgency was found to be uniquely relevant to clinical measures in the BD + AD group. Rapid cycling was associated with both urgency subscales and BIS-11 scores, and the Alcohol Dependence Scale was most correlated with the Premeditation subscale., Limitations: Cross sectional design and predominantly white sample., Conclusions: Unlike the BIS-11, UPPS-P is able to distinguish emotional from nonemotional facets of impulsivity, something especially relevant to people with co-occurring BD + AD, where fluid emotionality is a key part of symptom presentation. For this reason, the UPPS-P should be utilized in future studies and clinical settings measuring trait impulsivity in this population., (© 2024 Research Society on Alcohol.)

Objective: A social-cognitive perspective on posttraumatic stress disorder (PTSD) has been proposed and posits that impaired social cognition, rooted in attachment insecurity, plays a role in the development of PTSD. Support for the role of impaired social cognition in PTSD has been found in adults, but the social-cognitive perspective on PTSD has not been examined in adolescents. This study sought to explore differences in social cognition and PTSD on the basis of attachment security, and it examined social cognition as a mediator in the relation between attachment security and PTSD and with regard to PTSD symptom change during inpatient treatment., Method: We recruited 142 adolescents from an inpatient psychiatric hospital, where adolescents and their parents completed assessments at admission and discharge., Results: Adolescents with a secure attachment demonstrated better social-cognitive skills than did those with an insecure attachment. Social cognition mediated the relation between adolescents' maternal attachment representations and PTSD at admission across 3 self- and parent-report measures. Social cognition also mediated the relation between adolescents' maternal attachment representations at admission and PTSD treatment outcome., Conclusion: This study provides the 1st support for the application of Sharp, Fonagy, and Allen's (2012) social-cognitive perspective of PTSD to adolescents by showing a link between clinically significant symptoms of PTSD and attachment security through social-cognitive impairment. Findings indicate that improvement in PTSD during medium-stay inpatient treatment is partially driven by baseline attachment security and social-cognitive abilities, highlighting the potential of social-cognitive skills as important targets of clinical intervention among adolescents with PTSD. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Traditional social-cognitive approaches for investigating interpersonal problems in adolescent depression are limited. An important functional domain studied in adolescent depression is reward, but experimental paradigms have largely been non-social. In this paper, we propose the methods and concepts of neuroeconomics may address this gap. We begin by discussing a well-established social reward model for vulnerability to adolescent depression. We then show how neuroeconomics may extend this model by offering the tools to examine the mechanics of social exchanges, in behavioral and neural terms, that maintain (or pose vulnerability to) depression. In doing so, we propose a neureoconomic model of adolescent depression in which depression is defined as a perturbation of interpersonal motivational/reward exchange. This model serves to guide future research.