The neurobiology of impulsivity and substance use disorders: implications for treatment

Coles A.S., Kozak K., George T.P.

Substance use disorders (SUDs) are a leading cause of disability worldwide. While several pharmacological and behavioral treatments for SUDs are available, these may not be effective for all patients. Recent studies using non-invasive neuromodulation techniques including Repetitive Transcranial Magnetic Stimulation (rTMS), Transcranial Direct Current Stimulation (tDCS), and Deep Brain Stimulation (DBS) have shown promise for SUD treatment.Multiple studies were evaluated investigating the therapeutic potential of non-invasive brain stimulation techniques in treatment of SUDs.Through literature searches (eg, PubMed, Google Scholar), 60 studies (2000-2017) were identified examining the effect of rTMS, tDCS, or DBS on cravings and consumption of SUDs, including tobacco, alcohol, cannabis, opioids, and stimulants.rTMS and tDCS demonstrated decreases in drug craving and consumption, while early studies with DBS suggest similar results. Results are most encouraging when stimulation is targeted to the Dorsolateral Prefrontal Cortex (DLPFC).Short-term treatment with rTMS and tDCS may have beneficial effects on drug craving and consumption. Future studies should focus on extending therapeutic benefits by increasing stimulation frequency and duration of treatment.The utility of these methods in SUD treatment and prevention are unclear, and warrants further study using randomized, controlled designs. (Am J Addict 2018;27:71-91).

Anton R.F., Schacht J.P., Voronin K.E., Randall P.K.

Aspects of impulsivity have been implicated in the development, or maintenance, of alcohol use disorder (AUD). The brain dopamine system is implicated in both reward processing/memory (typically subcortical) and in brain inhibitory control mechanisms (typically cortical). Using a validated clinical laboratory paradigm, the dopamine/serotonin "stabilizing" drug, aripiprazole was evaluated in non-treatment-seeking AUD individuals based on their level of impulsivity/self-control.Ninety-nine individuals (77% male; mean age 27; 7.5 drinks per day; 83% heavy drinking days) meeting DSM-IV criteria for alcohol dependence were randomized to aripiprazole (N = 47 evaluable) or placebo (N = 48 evaluable) based on their Barratt Impulsiveness Scale (BIS-11) score (above or below 68). Aripiprazole, or similar placebo, was titrated to 15 mg over 8 days. Drinking was recorded over 6 days under natural conditions. On Day 8, after 1 day of required abstinence, individuals participated in a bar laboratory paradigm that included a priming drink (breath alcohol concentration [BAC] target 0.02 to 0.03 g/dl) and free-choice consumption of up to 8 drinks (max BAC 0.1 g/dl) in exchange for a "bar credit" of $2 per drink (max $16). End points were drinks per day under natural conditions and drinks consumed in the bar laboratory after the priming drink.There was no significant main effect of aripiprazole or interaction with BIS-11 score during the natural drinking period. However, there was a main effect of aripiprazole on bar laboratory drinking (p = 0.04) and aripiprazole reduced the total number of drinks consumed more among individuals with low self-control (p = 0.034) and increased latency to consume those drinks (p = 0.045) more among those with high impulsivity. Relative to placebo, aripiprazole caused more side effects and increased alcohol-induced sedation, but neither significantly influenced its interaction with impulsivity/self-control scores on drinking.This paradigm forced a choice between immediate drinking reward and delayed monetary reward. In those with high impulsivity and/or low self-control, aripiprazole shifts the balance away from immediate drinking toward a later reward. Medications targeting cortical dopamine/serotonin balance might show clinical benefit of reduced drinking, among individuals with impulsivity/low self-control.

Ficarella S.C., Battelli L.

Action inhibition is a complex decision process that can be triggered by external factors (exogenous) or internal decisions (endogenous). While the neuronal underpinnings of exogenous action inhibition have been extensively investigated, less is known about the brain areas responsible for endogenous action inhibition.We used inhibitory repetitive transcranial magnetic stimulation (rTMS) to test the causal role of two brain areas, the left dorsal fronto-median Cortex (dFMC) and the right Inferior Frontal Cortex (rIFC) in exogenous and endogenous action inhibition.The exogenous condition was a modified version of the Go/NoGo paradigm, where a green stimulus served as a cue to perform an action (a button press, Exogenous-Go), while a magenta stimulus indicated that action should be withhold (Exogenous-NoGo). Crucially, for the endogenous condition we psychophysically generated a shade of colour that participants randomly categorized as green or magenta. This unique stimulus, randomly intermixed with green and magenta stimuli, forced participants to perform an endogenous (internally-driven) choice to either execute or inhibit the action.In the endogenous condition, at baseline participants executed the action on half the trials; however, after 1-Hz rTMS over the dFMC they responded significantly more frequently, indicating a reduced response inhibition. The effect was selective for the dFMC stimulation and sustained in time. Moreover, no significant effects were found in the exogenous condition.These results support the causal role of the left dFMC in endogenous action inhibition and, more generally, the notion of separate brain circuits for endogenous and exogenous action inhibition.

Rochat L., Billieux J., Gagnon J., Van der Linden M.

Risky and excessive behaviors, such as aggressive and compulsive behaviors, are frequently described in patients with brain damage and have dramatic psychosocial consequences. Although there is strong evidence that impulsivity constitutes a key factor at play in these behaviors, the literature about impulsivity in neuropsychology is to date scarce. In addition, examining and understanding these problematic behaviors requires the assumption that impulsivity is a multidimensional construct. Consequently, this article aims at shedding light on frequent risky and excessive behaviors in patients with brain damage by focusing on a unified, comprehensive, and well-validated model, namely, the UPPS model of impulsivity. This model considers impulsivity as a multidimensional construct that includes four facets: urgency, (lack of) premeditation, (lack of) perseverance, and sensation seeking. Furthermore, we discuss the psychological mechanisms underlying the dimensions of impulsivity, as well as the laboratory tasks designed to assess each mechanism and their neural bases. We then present a scale specifically designed to assess these four dimensions of impulsivity in patients with brain damage and examine the data regarding this multidimensional approach to impulsivity in neuropsychology. This review supports the need to adopt a multifactorial and integrative approach toward impulsive behaviors, and the model presented provides a valuable rationale to disentangle the nature of brain systems and mechanisms underlying impulsive behaviors in patients with brain damage. It may also foster further relevant research in the field of impulsivity and improve assessment and rehabilitation of impulsive behaviors in clinical settings.

Brooks S.J., Wiemerslage L., Burch K., Maiorana S., Cocolas E., Schiöth H., Kamaloodien K., Stein D.

Impulsivity is a vulnerability trait for poor self-regulation in substance use disorder (SUD). Working memory (WM) training improves impulsivity and self-regulation in psychiatric disorders. Here we test WM training in methamphetamine use disorder (MUD). There are 15 MUD patients receiving inpatient treatment as usual (TAU) and 20 who additionally completed WM cognitive training (CT) and 25 healthy controls (HC). MANCOVA repeated measures analyses examined changes in impulsivity and self-regulation at baseline and after 4 weeks. Post hoc t tests confirmed that at baseline, feelings of self-control were significantly lower in the MUD (t = 2.001, p = 0.05) and depression was higher (t = 4.980, p = 0.001), as was BIS total impulsivity (t = 5.370, p = 0.001) compared to the HC group. Total self-regulation score was higher in HC than MUD patients (t = 5.370, p = 0.001). CT had a 35% learning rate (R 2 = 0.3523, p < 0.05). Compared to follow-up TAU, follow-up CT group had higher self-reported mood scores (t = 2.784, p = 0.01) and higher compared to CT baseline (t = 2.386, p = 0.036). Feelings of self-control were higher in CT than TAU at follow-up (t = 2.736, p = 0.012) and also compared to CT baseline (t = 3.390, p = 0.006), lack of planning significantly improved in CT between baseline and follow-up (t = 2.219, p = 0.048), as did total impulsivity scores (t = 2.085, p = 0.048). Measures of self-regulation were improved in the CT group compared to TAU at follow-up, in total score (t = 2.442, p = 0.038), receiving score (t = 2.314, p = 0.029) and searching score (t = 2.362, p = 0.027). Implementing self-regulation was higher in the CT group compared to TAU (t = 2.373, p = 0.026). WM training may improve control of impulsivity and self-regulation in people with MUD.

Kozak K., Barr M.S., George T.P.

The most common addictions in schizophrenia include tobacco, cannabis, alcohol, stimulants/recreational drugs, and gambling. This review discusses the multifactorial risk factors for addictions in people with schizophrenia. Several hypotheses have been proposed to explain addiction comorbidity in schizophrenia, and potential biomarkers conferring addiction risk in patients have been identified (e.g., catechol-O-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF), v-akt murine thymoma viral oncogene homolog 1 (AKT1), cortical inhibition, working memory). Neurotransmitter systems including dopaminergic, glutamatergic, and GABAergic pathways are associated with the pathophysiology of both schizophrenia and addictions. Developing effective treatments for schizophrenia and comorbid addictions is warranted and should involve further studies of neurobiological underpinnings of addiction risk in schizophrenia.

Brevet-Aeby C., Brunelin J., Iceta S., Padovan C., Poulet E.

Impulsivity has been reported in many psychiatric conditions and includes deficits in several cognitive functions such as attention, inhibitory control, risk taking, delay discounting and planning. Many studies have shown that noninvasive brain stimulation (NIBS) techniques modulate the activity of the prefrontal cortex and the functions involved in impulsivity.This article aims to review the literature on the effect of NIBS on impulsivity in healthy subjects aged 18-65 years old, and to highlight research avenues to develop therapeutic alternatives for such disorders.We performed a systematic review of the literature in the PubMed database following PRISMA method with "transcranial magnetic stimulation", "repetitive transcranial magnetic stimulation", "transcranial direct current stimulation", "inhibition", "risk", "impulsive behavior", "attention", "reward", "delay discounting", "delay task", "planning", "prefrontal cortex" as key words.We selected fifty-six studies showing modulation of the cognitive functions involved in impulsivity through NIBS.The data led us to consider new therapeutic alternatives in impulsive disorders by modulating prefrontal cortex activity through NIBS.

Shen B., Yin Y., Wang J., Zhou X., McClure S.M., Li J.

In intertemporal choice (ITC), people discount future rewards in proportion to the time delay until reward receipt. Despite recent non-invasive brain stimulation studies suggesting a general causal link between dorsolateral prefrontal cortex (dlPFC) activity and ITC impulsivity, results regarding the functional specificity of dlPFC are mixed. We used high-definition transcranial direct current stimulation (HD-tDCS) to map changes in causal impulsivity through bi-directional modulation of left and right dlPFC during ITC. Model-free and model-based analyses demonstrated that anodal and cathodal stimulation of left dlPFC, but not right dlPFC, decreased and increased impulsivity, respectively. Critically, an individual differences analysis revealed that modulation of impulsivity was contingent on participants' baseline impulsivity. Overall, our results might reconcile the discrepancies in the existing literature and suggest a baseline-dependent role for left dlPFC during ITC.

Zack M., Cho S.S., Parlee J., Jacobs M., Li C., Boileau I., Strafella A.

Repeated transcranial magnetic stimulation (rTMS) can reduce cravings and improve cognitive function in substance dependent individuals. Whether these benefits extend to individuals with pathological gambling (PG) is unclear. High-frequency rTMS of the medial prefrontal cortex (PFC) and continuous theta burst stimulation (cTBS) of the right dorsolateral PFC can reduce impulsive choice in healthy volunteers.This study aimed to assess the effects of these two protocols on gambling reinforcement and related responses in otherwise healthy men with PG.Participants (n = 9) underwent active or sham treatments at weekly intervals in a repeated-measures, Latin square design. Subjective and physiological responses were assessed before and after a 15-min slot machine game on each session. Delay discounting and Stroop tasks measured post-game impulsive choice and attentional control.Multivariate analysis of covariance, controlling for winnings on the slot machine under each treatment, found that rTMS reduced the post-game increase in Desire to Gamble; cTBS reduced amphetamine-like effects, and decreased diastolic blood pressure. Treatment had no significant univariate effects on bet size or speed of play in the game; however, a multivariate effect for the two indices suggested that treatment decreased behavioral activation. Neither treatment reduced impulsive choice, while both treatments increased Stroop interference.rTMS and cTBS can reduce gambling reinforcement in non-comorbid men with PG. Separate processes appear to mediate gambling reinforcement and betting behavior as against delay discounting and Stroop interference. Interventions that modify risky as opposed to temporal aspects of decision making may better predict therapeutic response in PG.

Tomko R.L., Bountress K.E., Gray K.M.

Theoretically, substance use disorder (SUD) treatment that matches an individual's etiology and/or maintaining factors should be more effective than a treatment that does not directly address these factors. Impulsivity and sensation/reward seeking may contribute to the development and maintenance of SUDs, and are potential candidate variables for assigning patients to treatment. The goal is to identify whether current research can provide insight into which treatments may be most effective for individuals high in impulsivity or sensation seeking, relative to other treatments. A secondary goal is to provide recommendations for personalizing SUD treatment based on etiology or maintaining factors.This review summarizes clinical trials that speak to the differential effectiveness of two or more treatments for alcohol, tobacco, and other drug use disorders, based on pre-treatment impulsivity, sensation seeking, or related constructs.Few studies examine the differential effectiveness of two or more treatments for individuals high in impulsivity or sensation seeking. Very preliminary evidence suggests that contingency management may hold promise for individuals high in impulsivity. Pharmacological trials were under-represented in the current review, despite evidence that the effectiveness of some pharmacological interventions may be moderated by impulsivity.Potential reasons for slow rate of progress to date are provided. Given slow accumulation of evidence, an alternative method for personalizing treatment based on pre-treatment psychosocial factors, including impulsivity and sensation/reward seeking, is proposed. Future research may explore the role of contingency management for SUD among individuals with high pre-treatment impulsivity or sensation seeking. Finally, novel, technology-enhanced behavioral mechanisms are discussed as an adjunct to SUD treatment for these high-risk populations.

MacKillop J., Weafer J., C. Gray J., Oshri A., Palmer A., de Wit H.

Impulsivity has been strongly linked to addictive behaviors, but can be operationalized in a number of ways that vary considerably in overlap, suggesting multidimensionality. This study tested the hypothesis that the latent structure among multiple measures of impulsivity would reflect the following three broad categories: impulsive choice, reflecting discounting of delayed rewards; impulsive action, reflecting ability to inhibit a prepotent motor response; and impulsive personality traits, reflecting self-reported attributions of self-regulatory capacity. The study used a cross-sectional confirmatory factor analysis of multiple impulsivity assessments. Participants were 1252 young adults (62 % female) with low levels of addictive behavior, who were assessed in individual laboratory rooms at the University of Chicago and the University of Georgia. The battery comprised a Delay (replace hyphen with space) Discounting Task, Monetary Choice Questionnaire, Conners’ Continuous Performance Test, Go/NoGo Task, Stop Signal Task, Barratt Impulsiveness Scale, and the UPPS-P Impulsive Behavior Scale. The hypothesized three-factor model provided the best fit to the data, although sensation seeking was excluded from the final model. The three latent factors were largely unrelated to each other and were variably associated with substance use. These findings support the hypothesis that diverse measures of impulsivity can broadly be organized into three categories that are largely distinct from one another. These findings warrant investigation among individuals with clinical levels of addictive behavior and may be applied to understanding the underlying biological mechanisms of these categories.

Smith G.T., Cyders M.A.

The personality traits of positive and negative urgency refer to the tendencies to act rashly when experiencing unusually positive or negative emotions, respectively.The authors review recent empirical work testing urgency theory (Cyders and Smith, 2008a) and consider advances in theory related to these traits.Empirical findings indicate that (a) the urgency traits are particularly important predictors of the onset of, and increases in, substance use in both children and young adults; (b) they appear to operate in part by biasing psychosocial learning; (c) pubertal onset is associated with increases in negative urgency, which in turn predict increases in adolescent drinking behavior; (d) variation in negative urgency trait levels are associated with variations in the functioning of an identified brain system; and (e) variations in the serotonin transporter gene, known to influence the relevant brain system, relate to variations in the urgency traits.A recent model (Carver et al., 2008) proposes the urgency traits to be markers of a tendency to respond reflexively to emotion, whether through impulsive action or ill-advised inaction (the latter leading to depressive symptoms); this model has received empirical support. The authors discuss new directions for research on the urgency traits.

Reed S.C., Evans S.M.

Effective treatments for cocaine use disorders remain elusive. Two factors that may be related to treatment failures are route of cocaine used and impulsivity. Smoked cocaine users are more likely to have poorer treatment outcomes compared to intranasal cocaine users. Further, cocaine users are impulsive and impulsivity is associated with poor treatment outcomes. While stimulants are used to treat Attention Deficit Hyperactivity Disorder (ADHD) and attenuate certain cocaine-related behaviors, few studies have comprehensively examined whether stimulants can reduce behavioral impulsivity in cocaine users, and none examined route of cocaine use as a factor.The effects of immediate release oral d-amphetamine (AMPH) were examined in 34 cocaine users (13 intranasal, 21 smoked). Participants had three separate sessions where they were administered AMPH (0, 10, or 20mg) and completed behavioral measures of impulsivity and risk-taking and subjective measures of abuse liability.Smoked cocaine users were more impulsive on the Delayed Memory Task, the GoStop task and the Delay Discounting Task than intranasal cocaine users. Smoked cocaine users also reported more cocaine craving and negative mood than intranasal cocaine users. AMPH produced minimal increases on measures of abuse liability (e.g., Drug Liking).Smoked cocaine users were more impulsive than intranasal cocaine users on measures of impulsivity that had a delay component. Additionally, although AMPH failed to attenuate impulsive responding, there was minimal evidence of abuse liability in cocaine users. These preliminary findings need to be confirmed in larger samples that control for route and duration of cocaine use.

Nuijten M., Blanken P., Van den Brink W., Goudriaan A.E., Hendriks V.M.

Background: High impulsivity and attentional bias are common in cocaine-dependent patients and predict poor treatment outcomes. The pharmacological agent modafinil is studied for its cognitive-enhancing capacities and may therefore improve clinical outcomes in crack-cocaine dependent patients. In this study, we investigated first whether pre-treatment impulsivity and attentional bias predict treatment outcome; next whether the drug modafinil given as an add-on treatment to cognitive behavioural therapy (CBT) improves impulsivity and attentional bias; and last, whether changes in impulsivity and attentional bias are related to improvements in treatment outcome. Methods: Crack-cocaine dependent outpatients ( n = 65) were randomised to 12 weeks CBT plus modafinil (400 mg/day) or only CBT. Self-reported impulsivity was assessed at baseline using the Barratt Impulsiveness Scale. At baseline and Week 12, we assessed inhibitory control as a behavioural measure of impulsivity, in terms of cognitive interference (Stroop task) and response inhibition (‘stop-signal task’), and attentional bias with the addiction Stroop task. Clinical outcomes were CBT-retention and crack-cocaine use. Results: At baseline, self-reported impulsivity predicted better CBT-retention; low self-reported and behavioural impulsivity and attentional bias predicted less crack-cocaine use. Changes in cognitive performance were not modafinil-related, but most likely due to low adherence. Improvements in impulsivity or attentional bias were not associated with CBT-retention nor changes in crack-cocaine use. Conclusions: Baseline impulsivity and attentional bias predicted clinical outcomes in crack-cocaine dependent patients. There were no firm indications that modafinil reduced impulsivity nor attentional bias in this population. Future studies involving cognitive-enhancing medications should include strategies to optimise adherence, to be better able to evaluate their potential.

Chester D.S., Lynam D.R., Milich R., Powell D.K., Andersen A.H., DeWall C.N.

Self-control often fails when people experience negative emotions. Negative urgency represents the dispositional tendency to experience such self-control failure in response to negative affect. Neither the neural underpinnings of negative urgency nor the more general phenomenon of self-control failure in response to negative emotions are fully understood. Previous theorizing suggests that an insufficient, inhibitory response from the prefrontal cortex may be the culprit behind such self-control failure. However, we entertained an alternative hypothesis: negative emotions lead to self-control failure because they excessively tax inhibitory regions of the prefrontal cortex. Using fMRI, we compared the neural activity of people high in negative urgency with controls on an emotional, inhibitory Go/No-Go task. While experiencing negative (but not positive or neutral) emotions, participants high in negative urgency showed greater recruitment of inhibitory brain regions than controls. Suggesting a compensatory function, inhibitory accuracy among participants high in negative urgency was associated with greater prefrontal recruitment. Greater activity in the anterior insula on negatively-valenced, inhibitory trials predicted greater substance abuse one month and one year after the MRI scan among individuals high in negative urgency. These results suggest that, among people whose negative emotions often lead to self-control failure, excessive reactivity of the brain's regulatory resources may be the culprit.

Shannon H., Montgomery M., Guimond S., Hellemans K.

Kurtin D.L., Prabhu A.M., Hassan Q., Groen A., Amer M.J., Lingford-Hughes A., Paterson L.M.

Boparai K., Lin H., Selby P., Zawertailo L.

Simandl G., Twining R.C., Raddatz N.J., Berentson G., Peck S., Wheeler R., Savtchouk I., Choi S., Baker D.A.

AbstractHuman cognitive abilities are deeply rooted in evolutionary building blocks that maximize computation while maintaining efficiency. These abilities are not without evolutionary signatures; conserved processes like vision have undergone continual phylogenetic adjustments to better serve ecological niches. Conversely, more sophisticated forms of cognition may have required evolutionary innovations to transform existing neuronal processing to expand computational abilities. One such innovation is system xc- (Sxc), a cystine-glutamate antiporter predominantly localized to astrocytes that emerged in deuterostomes (e.g., vertebrates) after their divergence from protostomes over 550 million years ago. Previous evidence suggests that genetically modified rats that lack functional Sxc (MSxc) exhibit enhanced cocaine-seeking behavior. In this study, we deconstructed drug-seeking into its component behaviors, categorizing them as reliant on evolutionary conserved or newly evolved cognitive processes. Our results reveal that Sxc function is dispensable for conserved processes like visual, emotional, and hedonic processing, but critical for advanced, evolutionary new cognitive functions, particularly impulse control and decision making. Notably, we demonstrate a temporally specific reliance on Sxc during the learning phase of optimal decision-making, but not in maintaining established strategies. This is an important addition to our current understanding of astrocytes in non-homeostatic functions, indicating their critical role in computationally demanding phases of learning and memory. Unraveling evolutionary innovations like Sxc not only deepens our understanding of cognitive evolution but also paves the way for revolutionary, precision- targeted therapies in neuropsychiatric disorders, potentially transforming treatment paradigms and patient outcomes.

Aviram-Friedman R., Alyagon U., Kafri L., Atias S., Zangen A.

Pardossi S., Cuomo A., Koukouna D., Pinzi M., Firenzuoli B., Fagiolini A.

Impulsivity is increasingly recognized as a transdiagnostic feature that spans multiple psychiatric disorders, including borderline personality disorder (BPD), bipolar disorder, and substance use disorders. In BPD, impulsive behaviors manifest as substance misuse, risky sexual activity, self-injury, and other maladaptive patterns. This review article updates the clinical and preclinical literature to explore the biological and psychological bases of impulsivity in BPD and considers whether methylphenidate (MPH) can be used as a treatment in this context. Although no medication is specifically approved for BPD, limited evidence from patients with comorbid BPD and attention-deficit/hyperactivity disorder (ADHD) indicates that MPH may reduce impulsivity and improve key symptoms. In addition, real-world data indicate that MPH may be associated with better outcomes and a lower risk of suicidal behaviors in patients with BPD. Nevertheless, such evidence remains scant, particularly among those with a primary diagnosis of BPD without a diagnosis of ADHD. Larger, methodologically rigorous studies are needed to clarify the efficacy and safety of MPH in targeting impulsivity within this population. An improved understanding of dopaminergic mechanisms may eventually shed light on MPH’s therapeutic role in BPD, although current data remain preliminary. Overall, recognizing impulsivity as a core symptom rather than focusing exclusively on diagnostic boundaries may facilitate more tailored and effective interventions for BPD.

Rezapour T., Nafissi N., Rafei P., Vassileva J., Ekhtiari H.

Jones M.B., Broadway D.E., Gimenez-Zapiola M., Jorge R.E.

Vilar-Ribó L., Hatoum A.S., Grotzinger A.D., Mallard T.T., Elson S., Fontanillas P., Palmer A.A., Gustavson D.E., Sanchez-Roige S.

Abstract Background Impulsivity is a multidimensional trait associated with substance use disorders (SUDs), but the relationship between distinct impulsivity facets and stages of substance use involvement remains unclear. Methods We used genomic structural equation modeling and genome-wide association studies (N = 79,729–903,147) to examine the latent genetic architecture of nine impulsivity traits and seven substance use (SU) and SUD traits. Results We found that the SU and SUD factors were strongly genetically inter-correlated (rG=0.77) but their associations with impulsivity facets differed. Lack of premeditation, negative and positive urgency were equally positively genetically correlated with both the SU (rG=.0.30–0.50) and SUD (rG=0.38–0.46) factors; sensation seeking was more strongly genetically correlated with the SU factor (rG=0.27 versus rG=0.10); delay discounting was more strongly genetically correlated with the SUD factor (rG=0.31 versus rG=0.21); and lack of perseverance was only weakly genetically correlated with the SU factor (rG=0.10). After controlling for the genetic correlation between SU/SUD, we found that lack of premeditation was independently genetically associated with both the SU (β=0.42) and SUD factors (β=0.21); sensation seeking and positive urgency were independently genetically associated with the SU factor (β=0.48, β=0.33, respectively); and negative urgency and delay discounting were independently genetically associated with the SUD factor (β=0.33, β=0.36, respectively). Conclusions Our findings show that specific impulsivity facets confer risk for distinct stages of substance use involvement, with potential implications for SUDs prevention and treatment.

Vasiliadis H., Lesage A., Rahme E., Rochette L., Gignac M., Massamba V., Diallo F.B., Fansi A., Cortese S., Lunghi C.

Roman M.L., Vansteene C., Poupon D., Gorwood P.

Agurto C., Cecchi G., King S., Eyigoz E.K., Parvaz M.A., Alia-Klein N., Goldstein R.Z.

Raji H., Dinesh S., Sharma S.

Abstract This abstract delves into the intricate nature of impulsivity and its ramifications across psychiatric disorders, leveraging advancements in neuroimaging and psychological studies. It elucidates diverse facets of impulsivity, encompassing response, choice, and tendencies, emphasizing its pivotal role in executive functioning and social development. The intricate interplay of hormonal influences, specifically cortisol, adrenaline, and testosterone, is meticulously examined, unveiling associations between elevated cortisol levels, excessive adrenaline release, and heightened impulsivity. The ventromedial prefrontal cortex (VMPFC) assumes a central role in decision-making and emotional regulation, demonstrating correlations with conditions, such as antisocial behavior and mood disorders. Substantial contributions from neurotransmitters like dopamine and serotonin to impulsive behavior underscore the imperative need for genetic and neurochemical investigations to identify factors crucial for effective management. Interconnections between stress, impulsivity, and decision-making are accentuated, particularly in mood disorders. Hormones, such as leptin and ghrelin, in conjunction with the hypothalamic–pituitary–adrenal axis, play pivotal roles in conditions like major depressive disorder. Concurrently, leptin resistance exerts influence over appetite and mood regulation. The nexus between impulsivity and substance use disorders emphasizes the intricate involvement of neurobiological, neurotransmitter, and genetic components, guiding targeted interventions. Recognition of gender-specific impulsive behaviors and hormonal influences is imperative for tailoring treatment plans. Advocating a comprehensive approach that integrates hormonal assessments with clinical evaluations, taking into account the neurobiological context, is essential. While serotonin systems show promise for treating impulsive aggressiveness, challenges encompass intricate hormonal interactions, ethical considerations, limited treatment options, and the necessity for individualized approaches. Addressing these intricacies is pivotal for advancing knowledge and formulating effective interventions for Impulsive Control Disorders.

Nagata J.M., Shim J., Low P., Ganson K.T., Testa A., He J., Santos G., Brindis C.D., Baker F.C., Shao I.Y.

Busch B.

Adult attention-deficit/hyperactivity disorder (ADHD) is a common precursor and comorbidity in those seeking treatment for substance use disorders (SUDs). Up to one in four patients with SUD may have comorbid ADHD. ADHD and SUD have common neurobiological features. Both ADHD and SUD have a chronic course, with severe functional impairments in educational, employment, interpersonal, and quality-of-life outcomes. Untreated childhood ADHD may lead to younger patient presentation with comorbid SUD+ADHD. The presence of ADHD increases the duration, severity, chronicity, and complexity of SUDs. Because treatment of comorbid ADHD can improve the ultimate outcomes for patients with SUD+ADHD, prompt screening and diagnosis of ADHD is important. Therefore, it is now recommended that SUD treatment programs: (1) include routine screening for ADHD in every initial SUD evaluation; and (2) perform a full diagnostic evaluation of ADHD, for those screening positive for ADHD. SUD treatment programs can increase their effectiveness by enhancing traditional care with 1) pharmacological treatment for ADHD, added to the SUD treatments already in use; and 2) cognitive-behavioral psychotherapy (CBT) specifically adapted to include ADHD-specific skills training (“integrated CBT”). Treatment for both conditions in those with SUD+ADHD is strongly recommended, with ADHD treatment starting as soon as the patient’s SUD is stabilized. Many excellent ADHD treatment options have demonstrated benefit to patients with SUD+ADHD. Abuse-resistant, extended-release stimulant medications demonstrate the best outcomes, and nonstimulant options have also shown success. Prescribers can do much to prevent stimulant medication misuse and diversion, while still offering first-line pharmacological treatment for ADHD. Recognition and treatment of comorbid SUD+ADHD ultimately improves SUD treatment retention and outcomes.