Michael A. Dawes

Etiology of early age onset substance use disorder: A maturational perspective

The etiology of early age onset substance use disorder (SUD), an Axis I psychiatric illness, is examined from the perspective of the multifactorial model of complex disorders. Beginning at conception, genetic and environment interactions produce a sequence of biobehavioral phenotypes during development which bias the ontogenetic pathway toward SUD. One pathway to SUD is theorized to emanate from a deviation in somatic and neurological maturation, which, in the context of adverse environments, predisposes to affective and behavioral dysregulation as the cardinal SUD liability-contributing phenotype. Dysregulation progresses via epigenesis from difficult temperament in infancy to conduct problems in childhood to substance use by early adolescence and to severe SUD by young adulthood.

Child abuse potential in parents with histories of substance use disorder.

OBJECTIVE To examine the relationship between parental history of substances use disorders (SUDs) and abuse potential. METHOD Milners (1986) Child Abuse Potential Inventory (CAPI) was administered to fathers and mothers (with and without histories of SUDs) of 10- to 12-year-old boys. RESULTS Fathers and mothers with lifetime histories of SUDs had higher Abuse Scale scores and were more likely to score in the Elevated range (as determined by clinically significant cutoff scores) than parents without such histories. No differences were found between parents with current diagnoses of SUD and those with past (but not current) histories of SUD. Fathers and mothers with a partner who had a history of SUD were more likely to score in the Elevated range, regardless of their own SUD histories. Separate regression models revealed that, for both fathers and mothers, emotional dysregulation (positive and negative affectivity) predicted Abuse Scale scores. Additional contributors to Abuse Scale scores were SUD status in fathers, and lack of involvement with the child in mothers. CONCLUSIONS History of SUDs in both fathers and mothers increases abuse potential. Contributors to abuse potential differed in fathers and mothers, underscoring the importance of examining parents separately in child maltreatment research.

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-tryptophans 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-tryptophans 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-tryptophans efficacy for treatment of psychiatric disorders, particularly when used in combination with other therapeutic agents.

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.

Developmental sources of variation in liability to adolescent substance use disorders

This review provides a synthesis of the literature on the complex sequence of maturational, psychosocial, and neuroadaptive processes that lead to substance use disorders (SUD) in adolescence. A brief overview introduces the concepts of liability to SUD and epigenesis. A theory is presented explaining how affective, cognitive, and behavioral dysregulation in late childhood is exacerbated during early and middle adolescence by family and peer factors, as well as puberty, leading to substance use. Continued exacerbation of the three components of dysregulation by drug and non-drug stressors during late adolescence is posited to result in neuroadaptations that increase the likelihood of developing SUD, particularly in high-risk individuals. Implications for etiologic research as well as clinical and preventive interventions are discussed.

Behavioral self-regulation: Correlates and 2 year follow-ups for boys at risk for substance abuse

This investigation demonstrated the heuristic construct of behavioral self-regulation (BSR) as a salient component of the liability to substance abuse. Three dimensions of childhood behaviour were employed to create a dimensional model of BSR: inattention, impulsivity/hyperactivity and aggressivity. Multiple measures and multiple informants were employed to develop indices of the three traits in a sample of 10-12 year old sons of substance abusing fathers (high risk (HR); n = 180) and normal controls (low average risk (LAR); n = 200). Informants included mothers, boys and their teachers. The results confirmed the presence of a first-order latent trait of BSR. HR boys had significantly higher scores on BSR than LAR boys. Concurrent validity of the BSR trait scores was supported by significant associations with measures of family dysfunction, deviant peer affiliations and poor school performance. These latter problems are commonly prodromal to substance abuse. Predictive validity of the BSR trait baseline scores (age 10-12 years) was supported at 2 year follow-up by significant associations of BSR scores with magnitude of deviant peer affiliations; trends toward significance were found for family dysfunction and poor school performance. Taken together, these results confirm and extend previous findings which indicate that poor BSR is prodromal to substance abuse.

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

RationaleMarijuana 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.ObjectivesThe 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.MethodsMarijuana-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.ResultsOf 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.ConclusionsThis 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.

Distinctions in Behavioral Impulsivity: Implications for Substance Abuse Research

ObjectivesResearchers have clearly implicated impulsivity as having a key role in substance use disorders, and comparisons of self-report measures suggest that there are measurably different components of impulsive behavior. However, comparatively little research has been devoted to understanding the multidimensional nature of this construct using laboratory measures of impulsivity that may be more sensitive to tracking changes across time. Many studies have measured impulsivity, but this construct has been measured using methodologically different types of laboratory impulsivity paradigms that are often used in isolation. As a result, it is important to determine whether some of the most frequently used types of behavioral measures of impulsivity account for unique variance. MethodsHere, we used factor analytical techniques in 2 studies to evaluate the independence of 3 of the most commonly used behavioral impulsivity paradigms. First, a factor analysis was conducted using previously collected data (n=204), and second, data were gathered specifically to replicate and extend the results of our original analysis (n=198). ResultsBoth studies revealed 3 distinct factors, confirming our hypothesis of at least 3 components of impulsive behavior that can be measured by these methodologic approaches. ConclusionsThese findings suggest that researchers should carefully consider their selection of laboratory behavioral impulsivity measures, and that the measure(s) selected should be related to the particular underlying processes relevant to substance use disorders and treatment success.

Effects of acute topiramate dosing on methamphetamine-induced subjective mood

Clinical studies have shown that topiramate, a sulphamate-substituted fructopyranose derivative, might be an efficacious treatment for alcohol dependence, smoking cessation within an alcohol-dependent population, and cocaine dependence. Mechanistically, topiramates therapeutic effects have been hypothesized to be due to inhibition of cortico-mesolimbic dopamine function, the primary substrate that governs the acquisition, maintenance, and reinstatement of goal-directed behaviour towards seeking abused drugs. Predicated on this hypothesis, we tested in 10 methamphetamine-dependent individuals (three females) whether low- or high-dose (15 or 30 mg i.v.) methamphetamine-induced positive subjective effects and reinforcement can be antagonized by low- or high-dose (100 or 200 mg orally) topiramate using a placebo-controlled, cross-over, factorial design. Methamphetamine administration was associated with orderly, prototypical, and significant increases on measures of stimulation, euphoria, craving, and reinforcement; however, some dysphoric symptoms also emerged. Topiramate alone showed a non-significant trend towards mild reductions in positive mood and reinforcement; yet topiramate appeared to accentuate the appreciation of methamphetamine-induced stimulation and euphoria significantly, but not craving or reinforcement. The experimental combination of topiramate and methamphetamine appeared to be safe and well tolerated, with few adverse events. Acute dosing with up to 200 mg topiramate appears to enhance, rather than attenuate, the positive subjective effects of methamphetamine. Perhaps this indicates a partial inhibition of methamphetamines reinforcing effects. Thus, testing chronically administered or higher doses, or both, of topiramate would be necessary to determine conclusively whether or not it can attenuate the positive subjective and reinforcing effects of methamphetamine.

Adolescent Suicidal Behavior and Substance Use: Developmental Mechanisms.

Adolescent suicidal behaviors and substance use are disturbingly common. Research suggests overlap of some of the etiological mechanisms for both adolescent suicidal behavior and substance use, yet clear understanding of the complex relations between these behaviors and their causal underpinnings is lacking. A growing body of evidence and a diathesis model (Mann et al. 1999; Mann, 2003) highlight the importance of impulse control as a proximal risk factor for adolescent suicidal and substance use behaviors. This literature review extends current theory on the relationships between adolescent suicidal behavior and substance use by: (1) examining how, when, and to what extent adolescent development is affected by poor impulse control, stressful life events, substance use behavior, and biological factors; (2) presenting proposed causal mechanisms by which these risk factors interact to increase risk for suicidal behaviors and substance use; and (3) proposing specific new hypotheses to extend the diathesis model to adolescents at risk for suicide and substance use. More specifically, new hypotheses are presented that predict bidirectional relationships between stressful life events and genetic markers of 5-HT dysregulation; substance use behavior and impulsivity; and substance use behavior and suicide attempts. The importance of distinguishing between different developmental trajectories of suicidal and substance use behaviors, and the effects of specific risk and protective mechanisms are discussed. Use of new statistical approaches that provide for the comparison of latent growth curves and latent class models is recommended to identify differences in developmental trajectories of suicidal behavior and substance use. Knowledge gained from these prospective longitudinal methods should lead to greater understanding on the timing, duration, and extent to which specific risk and protective factors influence the outcomes of suicidal behavior and substance use. In turn, findings from these studies should inform researchers who conduct future treatment and prevention studies.