Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Phylodynamics of HIV-1 from a Phase III AIDS Vaccine Trial in Bangkok, Thailand

In 2003, a phase III placebo-controlled trial (VAX003) was completed in Bangkok, Thailand. Of the 2,546 individuals enrolled in the trial based on high risk for infection through injection drug use (IDU), we obtained clinical samples and HIV-1 sequence data (envelope glycoprotein gene gp120) from 215 individuals who became infected during the trial. Here, we used these data in combination with other publicly available gp120 sequences to perform a molecular surveillance and phylodynamic analysis of HIV-1 in Thailand.Phylogenetic and population genetic estimators were used to assess HIV-1 gp120 diversity as a function of vaccination treatment, viral load (VL) and CD4(+) counts, to identify transmission clusters and to investigate the timescale and demographics of HIV-1 in Thailand. Three HIV-1 subtypes were identified: CRF01_AE (85% of the infections), subtype B (13%) and CRF15_AE (2%). The Bangkok IDU cohort showed more gp120 diversity than other Asian IDU cohorts and similar diversity to that observed in sexually infected individuals. Moreover, significant differences (P<0.02) in genetic diversity were observed in CRF01_AE IDU with different VL and CD4(+) counts. No phylogenetic structure was detected regarding any of the epidemiological and clinical factors tested, although high proportions (35% to 50%) of early infections fell into clusters, which suggests that transmission chains associated with acute infection play a key role on HIV-1 spread among IDU. CRF01_AE was estimated to have emerged in Thailand in 1984.5 (1983-1986), 3-6 years before the first recognition of symptomatic patients (1989). The relative genetic diversity of the HIV-1 population has remained high despite decreasing prevalence rates since the mid 1990s.Our study and recent epidemiological reports indicate that HIV-1 is still a major threat in Thailand and suggest that HIV awareness and prevention needs to be strengthened to avoid AIDS resurgence

Suicide in the United States Air Force: Risk factors communicated before and at death

Background: Over the last decade, suicide rates in the U.S. military have steadily increased, resulting in a call for suicide-related research with military populations. The present project aimed to describe and evaluate the communications (i.e., verbally and in suicide notes) of 13 suicide risk factors in the suicide death investigation files of 98 active duty U.S. Air Force (USAF) members. Methods: Two-hundred thirty-seven suicide death investigation files were coded. Ninety-eight decedents left suicide notes and were included in the current analyses. Descriptive statistics were computed to evaluate the types of risk factors most commonly communicated prior to and at the time of death as well as the medium for their communication. Specifically, verbal and note communications were compared to evaluate which medium decedents most often used to communicate risk factors. Also, the frequency that interpersonal compared to intrapsychic risk factors were communicated was evaluated. Results: Hopelessness (35.7% of cases) and perceived burdensomeness (31.6% of cases) were the risk factors most often communicated in suicide notes but not verbally. Thwarted belongingness (29.6% of cases) was the risk factor most often communicated verbally and in the suicide note. Further, evaluated risk factors were more frequently communicated in suicide notes than verbally. Finally, interpersonal risk factors were more often communicated than intrapsychic risk factors. Limitations: The validity of the data relies on interviews of decedents\u27 acquaintances and various medical/military records. Conclusions: Our findings support emphasizing certain risk factors over others in USAF suicide prevention efforts. Further, interpersonal risk factors appeared to be more salient than intrapsychic risk factors in the minds of decedents

Empirically informed approaches to topics in suicide risk assessment

The purpose of this article is to approach topics in suicide risk assessment from a scientifically informed standpoint. We summarize and elaborate a general framework for an empirically supported best practice recommendation in evaluating suicide potential and minimizing risk. This risk assessment framework provides a concise heuristic for assessment of suicidal symptoms, points the way to relatively routinized clinical decision-making and activity, and is compatible with best practices relevant to the legalities of suicide risk assessment. Having established a general and scientifically based framework for risk assessment, we go on to address the other questions noted above, with reference to the framework and to our ongoing scientific work. We conclude by summarizing all the work and providing clear and concise clinical recommendations based thereon. Copyright © 2004 John Wiley & Sons, Ltd

Empirically informed approaches to topics in suicide risk assessment

The purpose of this article is to approach topics in suicide risk assessment from a scientifically informed standpoint. We summarize and elaborate a general framework for an empirically supported best practice recommendation in evaluating suicide potential and minimizing risk. This risk assessment framework provides a concise heuristic for assessment of suicidal symptoms, points the way to relatively routinized clinical decision-making and activity, and is compatible with best practices relevant to the legalities of suicide risk assessment. Having established a general and scientifically based framework for risk assessment, we go on to address the other questions noted above, with reference to the framework and to our ongoing scientific work. We conclude by summarizing all the work and providing clear and concise clinical recommendations based thereon. Copyright © 2004 John Wiley & Sons, Ltd

Reconstructing Population History Using JC Virus: Amerinds, Spanish, and Africans in the Ancestry of Modern Puerto Ricans

The roots of the Hispanic populations of the Caribbean Islands and Central and South America go back to three continents of the Old World. In Puerto Rico major genetic contributions have come from (1) Asians in the form of the aboriginal Taino population, an Arawak tribe, present when Columbus arrived on the Island, (2) Europeans, largely Spanish explorers, settlers, government administrators, and soldiers, and (3) Africans who came as part of the slave trade. Since JC virus (JCV) genotypes characteristic of Asia, Europe, and Africa have been identified, and excretion of JCV in urine has been proposed as a marker for human migrations, we sought to characterize the JCV strains present in a Caribbean Hispanic population. We found that the strains of JCV present today in Puerto Rico are those derived from the Old World populations represented there: Types 1B and 4 from Spain, Types 3A, 3B, and 6 from Africa, and Type 2A from Asia. The Type 2A genotype represents the indigenous Taino people. This JCV genotype was represented much more frequently (61%) than would be predicted by the trihybrid model of genetic admixture. This might be attributable to characteristics of JCV Type 2A itself, as well as to the nature of the early relationships between Spanish men and native women. These findings indicate that the JCV strains carried by the Taino Indians can be found in today’s Puerto Rican population despite the apparent demise of these people more than two centuries ago. Therefore, molecular characterization of JCV provides a tool to supplement genetic techniques for reconstructing population histories including admixed populations

Emotion-related impulsivity and suicidal ideation: Towards a more specific model

Objectives Suicidal ideation is a pervasive and painful experience that varies considerably in its phenomenology. Here, we consider how one key risk variable might inform our understanding of variation in suicidal ideation: emotion-related impulsivity, the trait-like tendency towards unconstrained speech, behaviour, and cognition in the face of intense emotions. We hypothesized that emotion-related impulsivity would be tied to specific features, including severity, perceived lack of controllability, more rapidly fluctuating course, higher scores on a measure of acute suicidal affective disturbance, and more emotional and cognitive disturbance as antecedents. Methods We recruited two samples of adults (Ns = 421, 221) through Amazon Mechanical Turk (MTurk), with oversampling of those with suicidal ideation. Both samples completed psychometrically sound self-report measures online to assess emotion- and non-emotion-related dimensions of impulsivity and characteristics of suicidal ideation. Results One form of emotion-related impulsivity related to the severity, uncontrollability, dynamic course, and affective and cognitive precursors of ideation. Conclusions Despite limitations of the cross-sectional design and self-report measures, the current findings highlight the importance of specificity in considering key dimensions of impulsivity and suicidal ideation