Alcohol use disorder pharmacotherapy and treatment in primary care (ADaPT-PC) trial: Impact on identified barriers to implementation.

Background: A minority of individuals meeting diagnostic criteria for alcohol use disorders (AUD) receive any type of formal treatment. Developing options for AUD treatment within primary care settings is imperative to increase treatment access. A multi-faceted implementation intervention including provider and patient education, clinician reminders, development of local champions and ongoing facilitation was designed to enhance access to AUD pharmacotherapy in primary care settings at three large Veterans Health Administration (VHA) facilities. This qualitative study compared pre-implementation barriers to post-implementation barriers identified via provider interviews to identify those barriers addressed and not addressed by the intervention to better understand the limited impact of the intervention. Methods: Following the nine-month implementation period, primary care providers at the three participating facilities took part in qualitative interviews to collect perceptions regarding which pre-implementation barriers had and had not been successfully addressed by the intervention. Participants included 20 primary care providers from three large VHA facilities. Interviews were coded using common coding techniques for qualitative data using the Consolidated Framework for Implementation Research (CFIR) codebook. Summary reports were created for each CFIR construct for each facility and the impact of each CFIR construct on implementation was coded as positive, neutral, or negative. Results: Some barriers identified during pre-implementation interviews were no longer identified as barriers in the post-implementation interviews. These included Relative Advantage, Relative Priority, and Knowledge & Beliefs about the Innovation. However, Compatibility, Design Quality & Packaging, and Available Resources remained barriers at the end of the implementation period. No substantial new barriers were identified. Conclusions: The implementation intervention appears to have been successful at addressing barriers that could be mitigated with traditional educational approaches. However, the intervention did not adequately address structural and organizational barriers to implementation. Recommendations for enhancing future interventions are provided.

Adaptations to Opioid Use Disorder Care During the COVID-19 Pandemic: A National Survey of Prescribers.

OBJECTIVES: Among opioid use disorder (OUD)-treating providers, to characterize adaptations used to provide medications for OUD (MOUD) and factors associated with desire to continue virtual visits post-COVID-19 pandemic. METHODS: In a national electronic survey of OUD-treating prescribers (July-August 2020), analyses restricted to X-waivered buprenorphine prescribers providing outpatient, longitudinal care for adults with OUD, quantitative and qualitative analyses of survey items and free text responses were conducted. RESULTS: Among 797 respondents, 49% were men, 57% ≥50 years, 76% White, 68% physicians. Respondents widely used virtual visits to continue prescribing existing MOUD regimens (79%), provide behavioral healthcare (71%), and initiate new MOUD prescriptions (49%). Most prescribers preferred to continue/expand use of virtual visits after COVID-19. In multivariable models, factors associated with preference to continue/expand virtual visits to initiate MOUD postpandemic were treating a moderate number of patients prepandemic (aOR = 1.67; 95%[CI] = 1.06,2.62) and practicing in an urban setting (aOR = 2.17; 95%[CI] = 1.48,3.18). Prescribing buprenorphine prepandemic (aOR = 2.06; 95%[CI] = 1.11,3.82) and working in an academic medical center (aOR = 2.47; 95%[CI] = 1.30,4.68) were associated with preference to continue/expand use of virtual visits to continue MOUD postpandemic. Prescribing naltrexone extended-release injection prepandemic was associated with preference to continue/expand virtual visits to initiate and continue MOUD (aOR = 1.51; 95%[CI] = 1.10,2.07; aOR = 1.74; 95%[CI] = 1.19,2.54). Qualitative findings suggest that providers appreciated virtual visits due to convenience and patient accessibility, but were concerned about liability and technological barriers. CONCLUSIONS: Surveyed prescribers widely used virtual visits to provide MOUD with overall positive experiences. Future studies should evaluate the impact of virtual visits on MOUD access and retention and clinical outcomes.

Well-Being of Health Care Professionals Treating Opioid Use Disorder During the COVID-19 Pandemic: Results From a National Survey.

OBJECTIVE: The COVID-19 pandemic has dramatically affected health care delivery, effects that are juxtaposed with health care professional (HCP) burnout and mental distress. The Opioid Use Disorder Provider COVID-19 Survey was conducted to better understand the impact of COVID-19 on clinical practice and HCP well-being. METHODS: The cross-sectional survey was e-mailed to listservs with approximately 157,000 subscribers of diverse professions between July 14 and August 15, 2020. Two dependent variables evaluated HCP functioning and work-life balance. Independent variables assessed organizational practices and HCP experiences. Covariates included participant demographic characteristics, addiction board certification, and practice setting. Multilevel multivariate logistic regression models were used. RESULTS: Among 812 survey respondents, most were men, White, and physicians, with 46% located in urban settings. Function-impairing anxiety was reported by 17%, and 28% reported more difficulty with work-life balance. Difficulty with functioning was positively associated with having staff who were sick with COVID-19 and feeling close to patients, and was negatively associated with being male and having no staff changes. Difficulty with work-life balance was positively associated with addiction board certification; working in multiple settings; having layoffs, furloughs, or reduced hours; staff illness with COVID-19; and group well-being check-ins. It was negatively associated with male gender, older age, and no staff changes. CONCLUSIONS: Demographic, provider, and organizational-practice variables were associated with reporting negative measures of well-being during the COVID-19 pandemic. These results should inform HCPs and their organizations on factors that may lead to burnout, with particular focus on gender and age-related concerns and the role of well-being check-ins.

A Comparison of Cognitive Processing Therapy and Seeking Safety for the Treatment of Posttraumatic Stress Disorder in Veterans.

To compare the outcomes of Seeking Safety (SS) and cognitive processing therapy (CPT) in veterans with PTSD in a specialty clinic of an urban VA medical center. Retrospective chart review of electronic medical records was conducted for 420 veterans with PTSD who received treatment with either CPT (n = 227) or SS (n = 193) in group setting. 1) treatment completion rate, 2) self-reported PTSD symptom severity measured by PTSD checklist (PCL), and 3) additional mental health services received within 12 months after treatment. Data were analyzed for the 160 who had both a pre and post PCL documented in their charts. The final analysis sample included n = 94 for CPT and n = 66 for SS veterans with a mean age of 49.71[SD = 14] years, 24 women [15%]; mean baseline PCL score was 68.41 [9]. Significantly more veterans completed SS treatment (SS, 59 [89%] than CPT, 47 [50%] (p = <.001). However, PCL score decreases were significantly greater for patients who completed CPT treatment than those in SS (treatment x time interaction, 9.60 vs.4.98, respectively; difference, 4.62; t84 = 2.16; p = .02). The patients who received SS used significantly more mental health services of the PTSD clinical team than patients who completed CPT treatment (p = .01). The results of this study demonstrate the need for alternative approaches where dually diagnosed patients would not be delayed in their receipt of trauma-focused care - i.e., where treatment is initiated concurrently rather than sequentially to substance abuse treatment.

Studying molecular interactions in the intact organism: fluorescence correlation spectroscopy in the living zebrafish embryo.

Cell behaviour and function is determined through the interactions of a multitude of molecules working in concert. To observe these molecular dynamics, biophysical studies have been developed that track single interactions. Fluorescence correlation spectroscopy (FCS) is an optical biophysical technique that non-invasively resolves single molecules through recording the signal intensity at the femtolitre scale. However, recording the behaviour of these biomolecules using in vitro-based assays often fails to recapitulate the full range of variables in vivo that directly confer dynamics. Therefore, there has been an increasing interest in observing the state of these biomolecules within living organisms such as the zebrafish Danio rerio. In this review, we explore the advancements of FCS within the zebrafish and compare and contrast these findings to those found in vitro.

Implementing alcohol use disorder pharmacotherapy in primary care settings: a qualitative analysis of provider-identified barriers and impact on implementation outcomes.

BACKGROUND: Despite the high prevalence of alcohol use disorders (AUDs), in 2016, only 7.8% of individuals meeting diagnostic criteria received any type of AUD treatment. Developing options for treatment within primary care settings is imperative to increase treatment access. As part of a trial to implement AUD pharmacotherapy in primary care settings, this qualitative study analyzed pre-implementation provider interviews using the Consolidated Framework for Implementation Research (CFIR) to identify implementation barriers. METHODS: Three large Veterans Health Administration facilities participated in the implementation intervention. Local providers were trained to serve as implementation/clinical champions and received external facilitation from the project team. Primary care providers received a dashboard of patients with AUD for case identification, educational materials, and access to consultation from clinical champions. Veterans with AUD diagnoses received educational information in the mail. Prior to the start of implementation activities, 24 primary care providers (5-10 per site) participated in semi-structured interviews. Transcripts were analyzed using common coding techniques for qualitative data using the CFIR codebook Innovation/Intervention Characteristics, Outer Setting, Inner Setting, and Characteristics of Individuals domains. Number and type of barriers identified were compared to quantitative changes in AUD pharmacotherapy prescribing rates. RESULTS: Four major barriers emerged across all three sites: complexity of providing AUD pharmacotherapy in primary care, the limited compatibility of AUD treatment with existing primary care processes, providers' limited knowledge and negative beliefs about AUD pharmacotherapy and providers' negative attitudes toward patients with AUD. Site specific barriers included lack of relative advantage of providing AUD pharmacotherapy in primary care over current practice, complaints about the design quality and packaging of implementation intervention materials, limited priority of addressing AUD in primary care and limited available resources to implement AUD pharmacotherapy in primary care. CONCLUSIONS: CFIR constructs were useful for identifying pre-implementation barriers that informed refinements to the implementation intervention. The number and type of pre-implementation barriers identified did not demonstrate a clear relationship to the degree to which sites were able to improve AUD pharmacotherapy prescribing rate. Site-level implementation process factors such as leadership support and provider turn-over likely also interacted with pre-implementation barriers to drive implementation outcomes.

Effects of a multifaceted implementation intervention to increase utilization of pharmacological treatments for alcohol use disorders in the US Veterans Health Administration.

Over 16 million Americans meet diagnostic criteria for alcohol use disorder (AUD), but only 7.8% of them receive formal treatment each year. Safe and effective pharmacological treatments for AUD exist; however, they are rarely prescribed. Therefore, we developed and pilot tested a multifaceted implementation intervention to improve consideration and receipt of effective pharmacologic treatments for AUD, focusing on primary care settings where patients have the most frequent contact with healthcare systems. The intervention included training of local providers to serve as champions and a website for primary care providers that included educational materials, a case-finding dashboard, and contact information for local and national clinical experts. We also mailed patients educational material about treatment options. The intervention was implemented at three large facilities of the Veterans Health Administration (VHA). An interrupted time series design, analyzed with segmented logistic regression, was used to evaluate the intervention's effects. The odds of a patient with AUD receiving one of the AUD medications was increasing throughout the pre-implementation period, and the rate of change (slope) increased significantly in the implementation period. Translating these numbers into percentages, at baseline 2.9% of patients filled a prescription for an AUD medication within 30days of a primary care visit. This increased to 3.8% by the end of the pre-implementation period (increasing 0.037% per month), and increased to 5.2% by the end of the implementation period (increasing 0.142% per month). However, the intervention effect was not significant when control sites were added, suggesting that improvement may have been driven by secular trends rather than solely by this intervention. Although the intervention was feasible, it was not effective. Continued analysis of process and implementation data including qualitative interviews with key stakeholders, may elucidate the reasons this intervention was not successful and ways to strengthen its effects.

Enhancing access to alcohol use disorder pharmacotherapy and treatment in primary care settings: ADaPT-PC.

BACKGROUND: Only 7.8 % of individuals meeting diagnostic criteria for alcohol use disorder (AUD) receive treatment in a given year. Most individuals with AUDs are identified in primary care (PC) settings and referred to substance use disorders (SUD) clinics; however, only a minority of those referred attend treatment services. Safe and effective pharmacological treatments for AUD exist, but they are rarely prescribed by PC providers. The objective of this study is to refine, implement, and evaluate an intervention to integrate pharmacological AUD treatment options into PC settings. This paper provides a detailed description of the intervention design and the evaluation components. METHODS/DESIGN: Three large Veterans Health Administration (VHA) facilities are participating in the intervention. The intervention targets stakeholder groups with tailored strategies based on implementation theory and prior research identifying barriers to implementation of AUD pharmacotherapy. Local SUD providers and primary care mental health integration (PCMHI) providers are trained to serve as local implementation/clinical champions and receive external facilitation. PC providers receive access to consultation from local and national clinical champions, educational materials, and a dashboard of patients with AUD on their caseloads for case identification. Veterans with AUD diagnoses receive educational information in the mail just prior to a scheduled PC visit. Effectiveness of the intervention will be evaluated through an interrupted time series with matched controls to monitor change in facility level AUD pharmacotherapy prescribing rates. Following Stetler's four-phase formative evaluation (FE) strategy, FE methods include (1) developmental FE (pre-implementation interviews with champions, PC providers, and Veterans), (2) implementation-focused FE (tracking attendance at facilitation meetings, academic detailing efforts by local champions, and patient dashboard utilization), (3) progress-focused FE (tracking rates of AUD pharmacotherapy prescribing and rates of referral to PCMHI and SUD specialty care), and (4) interpretive FE (post-implementation interviews with champions and PC providers). Analysis of FE data will be guided by the Consolidated Framework for Implementation Research (CFIR). DISCUSSION: If demonstrated to be successful, this implementation strategy will provide a replicable, feasible, and relative low-cost method for integrating AUD treatment services into PC settings, thereby increasing access to AUD treatment.

Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study.

AIMS: To examine the safety and effectiveness of buprenorphine + naloxone sublingual tablets (BUP, as Suboxone(®) ) provided after administration of extended-release injectable naltrexone (XR-NTX, as Vivitrol(®) ) to reduce cocaine use in participants who met DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. METHODS: This multi-centered, double-blind, placebo-controlled study, conducted under the auspices of the National Drug Abuse Treatment Clinical Trials Network, randomly assigned 302 participants at sites in California, Oregon, Washington, Colorado, Texas, Georgia, Ohio, New York and Washington DC, USA to one of three conditions provided with XR-NTX: 4 mg/day BUP (BUP4, n = 100), 16 mg/day BUP (BUP16, n = 100, or no buprenorphine (placebo; PLB, n = 102). Participants received pharmacotherapy for 8 weeks, with three clinic visits per week. Cognitive behavioral therapy was provided weekly. Follow-up assessments occurred at 1 and 3 months post-intervention. The planned primary outcome was urine drug screen (UDS)-corrected, self-reported cocaine use during the last 4 weeks of treatment. Planned secondary analyses assessed cocaine use by UDS, medication adherence, retention and adverse events. RESULTS: No group differences were found between groups for the primary outcome (BUP4 versus PLB, P = 0.262; BUP16 versus PLB, P = 0.185). Longitudinal analysis of UDS data during the evaluation period using generalized linear mixed equations found a statistically significant difference between BUP16 and PLB [P = 0.022, odds ratio (OR) = 1.71] but not for BUP4 (P = 0.105, OR = 1.05). No secondary outcome differences across groups were found for adherence, retention or adverse events. CONCLUSIONS: Buprenorphine + naloxone, used in combination with naltrexone, may be associated with reductions in cocaine use among people who meet DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse.

Functional activation and effective connectivity differences in adolescent marijuana users performing a simulated gambling task.

Background. Adolescent marijuana use is associated with structural and functional differences in forebrain regions while performing memory and attention tasks. In the present study, we investigated neural processing in adolescent marijuana users experiencing rewards and losses. Fourteen adolescents with frequent marijuana use (>5 uses per week) and 14 nonuser controls performed a computer task where they were required to guess the outcome of a simulated coin flip while undergoing magnetic resonance imaging. Results. Across all participants, "Wins" and "Losses" were associated with activations including cingulate, middle frontal, superior frontal, and inferior frontal gyri and declive activations. Relative to controls, users had greater activity in the middle and inferior frontal gyri, caudate, and claustrum during "Wins" and greater activity in the anterior and posterior cingulate, middle frontal gyrus, insula, claustrum, and declive during "Losses." Effective connectivity analyses revealed similar overall network interactions among these regions for users and controls during both "Wins" and "Losses." However, users and controls had significantly different causal interactions for 10 out of 28 individual paths during the "Losses" condition. Conclusions. Collectively, these results indicate adolescent marijuana users have enhanced neural responses to simulated monetary rewards and losses and relatively subtle differences in effective connectivity.

Impulsivity, attention, memory, and decision-making among adolescent marijuana users.

RATIONALE: Marijuana is a popular drug of abuse among adolescents, and they may be uniquely vulnerable to resulting cognitive and behavioral impairments. Previous studies have found impairments among adolescent marijuana users. However, the majority of this research has examined measures individually rather than multiple domains in a single cohesive analysis. This study used a logistic regression model that combines performance on a range of tasks to identify which measures were most altered among adolescent marijuana users. OBJECTIVES: The purpose of this research was to determine unique associations between adolescent marijuana use and performances on multiple cognitive and behavioral domains (attention, memory, decision-making, and impulsivity) in 14- to 17-year-olds while simultaneously controlling for performances across the measures to determine which measures most strongly distinguish marijuana users from nonusers. METHODS: Marijuana-using adolescents (n = 45) and controls (n = 48) were tested. Logistic regression analyses were conducted to test for: (1) differences between marijuana users and nonusers on each measure, (2) associations between marijuana use and each measure after controlling for the other measures, and (3) the degree to which (1) and (2) together elucidated differences among marijuana users and nonusers. RESULTS: Of all the cognitive and behavioral domains tested, impaired short-term recall memory and consequence sensitivity impulsivity were associated with marijuana use after controlling for performances across all measures. CONCLUSIONS: This study extends previous findings by identifying cognitive and behavioral impairments most strongly associated with adolescent marijuana users. These specific deficits are potential targets of intervention for this at-risk population.

Acquisition of Rater Agreement for the Stressful Life Events Schedule.

Stress has been linked to a broad range of psychopathology including alcohol and drug dependence. Recent advances in our understanding of how stress interacts with biological systems involved in addiction has generated even greater interest in stress assessment among addiction researchers. The Stressful Life Events Schedule (SLES) capitalizes on the strengths and avoids the pitfalls of self-report checklist and interview-based stress assessments. Because the SLES depends on consensus ratings of a research team, this study examined rater agreement of stressful event ratings across the first year using the SLES. Individual ratings of stressful events were compared between two experienced and three new raters. Ratings were analyzed for life events generated from interviews of 70 adolescent psychiatric inpatients and 62 healthy adolescents. Inexperienced raters, with backgrounds in addiction research, reliably rated stressful events and rater agreement improved over a year's time. Recommendations for successfully adopting the SLES for consensus rating are discussed.

Preliminary Evidence for cue-induced Alcohol Craving Modulated by Serotonin Transporter Gene Polymorphism rs1042173.

We previously have shown that cue-induced alcohol craving and propensity for higher drinking are modulated by allelic differences in SLC6A4 associated with serotonin transporter (5-HTT) expression level alterations. In an independent study, we characterized another polymorphism, SNP rs1042173, in 3'-untranslated region (3'-UTR) of the same gene, which also altered 5-HTT expression levels; the T allele of rs1042173 was associated with lower mRNA and protein levels. In subsequent analyses, the TT genotype was found to be associated with higher drinking intensity in alcohol-dependent (AD) individuals of Caucasian descent. Building upon these findings, we hypothesized that the low-expressing TT genotype associated with intense drinking would predict higher craving for alcohol in AD individuals. In this pilot study, we sought to test our hypothesis by examining 34 Hispanic AD volunteers (mean age, 34.8 years) for rs1042173 genotype-based [i.e., TT versus TG/GG (Gx)] differences in subjective response to alcohol. We employed a human laboratory paradigm and analyzed the data using a linear mixed-effects model (SAS® PROC MIXED) to assess treatment, cue procedures, and genotype main effects as well as the two-way interaction effects between them. On subjective "urge to drink" and "crave for a drink," we found a significant main effect of the cue experiment (p ≤ 0.01) and an interaction effect between genotype and cue effects (p < 0.05). TT genotype was associated with higher urge to drink (p = 0.002) and crave for a drink (p = 0.005) when exposed to alcohol cue. Our results not only support the hypothesis that rs1042173 is a genetic marker for cue-induced alcohol craving among AD males but also are suggestive of a neurobiological mechanism associated with the rs1042173-TT genotype that triggers a disproportionate craving in response to alcohol consumption, which in turn may lead to more intense drinking. Future studies with larger sample sizes are needed to characterize the interactive effects of the serotonin transporter-linked polymorphic region (5'-HTTLPR)-L-allele reported in our previous study and of the rs1042173-TT genotype on cue-induced alcohol craving.

Intolerance to delayed reward in girls with multiple suicide attempts.

Impulsivity has been conceptualized as influencing the expression of suicidal behavior. Adolescence is a developmental period characterized both by a relatively high rate of suicide attempts and a high level of impulsivity. The current study examined two behavioral measures (delay reward and disinhibition) and one self-report measure of impulsivity among girls with suicide attempt histories. Girls with multiple suicide attempts performed more impulsively on measures of delayed reward, and had higher self-ratings of depression and aggression than girls with either one or no suicide attempts. The multiple attempter girls' preference for immediate gratification may directly increase vulnerability to suicidal acts in the context of distressing states or indirectly increase risk by creating poor life experience over time.

Failure to sustain prepulse inhibition in adolescent marijuana users.

BACKGROUND: Marijuana use is typically initiated during adolescence, which is a critical period for neural development. Studies have reported reductions in prepulse inhibition (PPI) among adults who use marijuana chronically, although no human studies have been conducted during the critical adolescent period. METHODS: This study tested PPI of acoustic startle among adolescents who were either frequent marijuana users or naïve to the drug (Controls). Adolescents were tested using two intensities of prepulses (70 and 85 dB) combined with a 105 dB startle stimulus, delivered across two testing blocks. RESULTS: There was a significant interaction of group by block for PPI; marijuana users experienced a greater decline in the PPI across the testing session than Controls. The change in PPI of response magnitude for users was predicted by change in urine THC/creatinine after at least 18 h of abstinence, the number of joints used during the previous week before testing, as well as self-reported DSM-IV symptoms of marijuana tolerance, and time spent using marijuana rather than participating in other activities. CONCLUSIONS: These outcomes suggest that adolescents who are frequent marijuana users have problems maintaining prepulse inhibition, possibly due to lower quality of information processing or sustained attention, both of may contribute to continued marijuana use as well as attrition from marijuana treatment.

Drinking histories in alcohol-use-disordered youth: preliminary findings on relationships to platelet serotonin transporter expression with genotypes of the serotonin transporter.

OBJECTIVE: The serotonin (5-HT) transporter (5-HTT) is thought to play a key role in the onset of alcohol use, with potential behavioral and biological mechanisms mediated by the level of 5-HT in the synapse and in cerebral spinal fluid. Although 5-HT dysregulation has been related to poor impulse control, the biological mechanism is unknown, although functional control of the serotonergic system has been shown to be regulated in part by differential expression of the 5-HTT. The gene responsible for encoding 5-HTT has a functional polymorphism at the 5'-regulatory promoter region, which results in two forms: long (L) and short (S). The LL genotype is hypothesized to play a key role in the early onset of alcohol use and may be related to poor impulse control. The objective of this pilot study is to determine whether adolescents with a current alcohol-use disorder (AUD) (N = 21) have platelet measures of the 5-HTT functioning that are related to 5-HTT genotype and poor impulse control. Specifically, we wanted to examine the relationships between the following: platelet 5-HTT and 5-HTT genotype; platelet 5-HTT parameters and age at onset, as well as duration of drinking; and 5-HTT genotype and impulse control. METHOD: Adolescents with current AUD were recruited from the community to participate in a cross-section pilot study. RESULTS: Our main findings showed significantly higher paroxetine binding (density of 5-HTT) in LL genotype versus S carriers (SS or SL genotypes); also, the LL group had a significantly earlier age at onset of drinking and longer duration of drinking, and poorer impulse control. CONCLUSIONS: These findings provide partial support for the hypothesis that, among currently drinking adolescents with an AUD, differential expression of 5-HTT may play an important role in the onset of adolescent AUD.

Impulsivity and clinical symptoms among adolescents with non-suicidal self-injury with or without attempted suicide.

This study examined clinical characteristics and laboratory-measured impulsive behavior of adolescents engaging in either non-suicidal self-injury with (NSSI+SA; n=25) or without (NSSI-Only; n=31) suicide attempts. We hypothesized that adolescent with NSSI+SI would exhibit more severe clinical symptoms and higher levels of behavioral impulsivity compared to adolescents with NSSI-Only. Adolescents were recruited from an inpatient psychiatric hospital unit and the two groups were compared on demographic characteristics, psychopathology, self-reported clinical ratings, methods of non-suicidal self-injury, and two laboratory impulsivity measures. Primary evaluations were conducted during psychiatric hospitalization, and a subset of those tested during hospitalization was retested 4-6 weeks after discharge. During hospitalization, NSSI+SA patients reported worse depression, hopelessness, and impulsivity on standard clinical measures, and demonstrated elevated impulsivity on a reward-directed laboratory measure compared to NSSI-Only patients. In the follow-up analyses, depression, hopelessness, suicidal ideation, and laboratory impulsivity were improved for both groups, but the NSSI+SA group still exhibited significantly more depressive symptoms, hopelessness, and impulsivity than the NSSI-Only group. Risk assessments for adolescents with NSSI+SA should include consideration not only of the severity of clinical symptoms but of the current level impulsivity as well.

Can serotonin transporter genotype predict craving in alcoholism?

BACKGROUND: We hypothesize that functional control of the serotonergic system is regulated in part by differential expression of the serotonin (5-HT) transporter (5-HTT). Alcohol-dependent individuals with the LL/LS genotype (L-carriers), compared with those with the SS genotype, have a lower 5-HT neurotransmission, which we hypothesize would be associated with higher craving for alcohol among L-carriers. We hypothesize further that acute peripheral depletion of tryptophan (5-HT's precursor), while further reducing 5-HT function, might decrease auto-inhibition of 5-HT neuronal firing, thereby increasing 5-HT neurotransmission transiently and lowering alcohol craving. METHODS: We tested these hypotheses by examining whether in 34 Hispanic alcohol-dependent individuals subjective and physiological cue craving for alcohol differed by genotype, age of onset of problem drinking, and tryptophan availability. RESULTS: On subjective "urge to drink" and "crave for a drink," we found a significant (p < 0.05) main effect of genotype and cue, as well as an interaction among genotype, age of onset of problem drinking, and tryptophan depletion. For the physiological measure of pulse, there was a main effect of genotype. L-carriers had higher craving than their SS counterparts, an effect that decreased under tryptophan depletion. While craving in L-carriers increased with an earlier age of onset of problem drinking, the opposite effect was seen in those with the SS genotype. CONCLUSION: These results not only provide support for the hypothesis that alcoholics who are L-carriers have greater alcohol craving and possibly greater propensity for drinking but also propose that there is an important 5-HTT gene-by-environment interaction that alters cue craving response for alcohol.

L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications.

An essential component of the human diet, L-tryptophan is critical in a number of metabolic functions and has been widely used in numerous research and clinical trials. This review provides a brief overview of the role of L-tryptophan in protein synthesis and a number of other metabolic functions. With emphasis on L-tryptophan's role in synthesis of brain serotonin, details are provided on the research uses of L-tryptophan, particularly L-tryptophan depletion, and on clinical trials that have been conducted using L-tryptophan supplementation. The ability to change the rates of serotonin synthesis in the brain by manipulating concentrations of serum tryptophan is the foundation of much research. As the sole precursor of serotonin, experimental research has shown that L-tryptophan's role in brain serotonin synthesis is an important factor involved in mood, behavior, and cognition. Furthermore, clinical trials have provided some initial evidence of L-tryptophan's efficacy for treatment of psychiatric disorders, particularly when used in combination with other therapeutic agents.