Amygdala Activation and Emotional Processing in Adolescents at Risk for Substance Use Disorders.

Studies are needed that examine neurobiological characteristics in high risk individuals prior to substance use disorder (SUD) development. In this pilot study, 4 adolescent subjects at high risk (having at least 1 parent with a SUD) for SUD were compared with 4 adolescent reference subjects on a corticolimbic reactivity paradigm, where they were presented with affect-laden faces or geometric shapes. FMRI was used to measure cortical activation in response to these stimuli. High risk subjects, compared to low risk, exhibited greater left amygdala activation (t=3.60, df=6, p=0.01), suggesting they may exhibit hyper-responsivity of the amygdala in response to emotional stimuli.

Psychological dysregulation, white matter disorganization and substance use disorders in adolescence.

AIMS: Adolescents with substance use disorders (SUD) have difficulties with cognitive, behavioral and affective regulation. White matter (WM) disorganization has been observed in adolescents with SUD and may be related to psychological dysregulation. This study compared adolescents with SUD and control adolescents to investigate relationships among psychological dysregulation, WM disorganization and SUD symptoms. DESIGN: Cross-sectional observation. SETTING: Adolescents with SUD were recruited from SUD treatment programs. Controls were recruited from the community. PARTICIPANTS: The 55 participants were aged 14-19; 35 with SUD and 20 controls without SUD. MEASUREMENTS: Psychological dysregulation was characterized by the Behavior Rating Inventory of Executive Function. WM disorganization was measured by diffusion tensor imaging, and fractional anisotropy, radial diffusivity and axial diffusivity were examined within cortical regions of interest. FINDINGS: Compared to controls, SUD adolescents showed significantly greater psychological dysregulation and prefrontal and parietal WM disorganization. WM disorganization was correlated positively with psychological dysregulation and cannabis-related symptoms. In multivariate mediation models, the results were consistent with both the neurodevelopmental immaturity model, in which WM disorganization leads to psychological dysregulation and cannabis-related symptoms, and with the substance effects model, in which cannabis-related symptoms lead to WM disorganization and psychological dysregulation. CONCLUSIONS: In adolescents, substance use disorder and psychological dysregulation appear to be associated with reduced frontoparietal network white matter maturation.

Gender differences in the relationship between white matter organization and adolescent substance use disorders.

Few studies have focused on the neurobiological correlates of adolescent-onset substance use disorders (SUDs), particularly with respect to white matter development and organization. This study investigated microstructural white matter characteristics associated with SUDs during the adolescent developmental period. Twenty-four case adolescents (ages 14-18) entering treatment for SUDs and 12 sex- and age-matched control adolescents with no psychopathology were compared. Diffusion tensor imaging data were collected and analyzed using the whole-brain tract-based spatial statistics (TBSS) method. In order to comprehensively characterize diffusivity characteristics, we first studied fractional anisotropy (FA), and within regions that differed in FA, other indicators of microstructure, including the axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). A large cluster of significantly lower FA values was found in cases compared to controls in the superior longitudinal fasciculus (SLF). Within this cluster, AD and RD were also significantly different between the groups, while MD was not significantly different. For FA, a significant group by sex interaction was found; females with SUD exhibited lower FA than males with SUD, while control females exhibited higher FA than control males. These results indicated significantly lower white matter integrity in the superior longitudinal fasciculus region of association cortex, and assessed using multiple indicators of diffusion. These findings suggest that the disruption of normal white matter development due to substance exposure may be more severe in females than in males.

Child abuse and other traumatic experiences, alcohol use disorders, and health problems in adolescence and young adulthood.

OBJECTIVE: We prospectively examined the health effects of child abuse and other traumatic events, with objective health indicators and consideration of alcohol use disorders (AUD). METHODS: Adolescents (n = 668) were recruited from clinical and community sources. At baseline, we examined child abuse and other traumas, AUD, health-related symptoms, physical findings, and blood assays. Subjects were assigned to Trauma Classes (TC), including witnessing violence, physical abuse, and sexual abuse. Health outcomes were again determined at 1-year and young adult follow-up. RESULTS: In adolescence, higher TC severity was associated with more health-related symptoms, increased age-adjusted body mass index, and stress-response immune system indices. In adolescence and young adulthood, the relationships between TC and health-related symptoms were mediated by anxiety. AUD was associated with liver injury, and cigarette smoking with heart/lung symptoms. CONCLUSIONS: Child abuse predicted persistently elevated health-related symptoms primarily attributable to anxiety, and early signs of liver disease were attributable to AUD.

Alcohol, psychological dysregulation, and adolescent brain development.

While adolescent alcohol consumption has been asserted to adversely alter brain development, research in human adolescents has not yet provided us with sufficient evidence to support or refute this position. Brain constituents actively developing during adolescence include the prefrontal cortex, limbic system areas, and white matter myelin. These areas serving cognitive, behavioral, and emotional regulation may be particularly vulnerable to adverse alcohol effects. Alternatively, deficits or developmental delays in these structures and their functions may underlie liability to accelerated alcohol use trajectories in adolescence. This review will describe a conceptual framework for considering these relationships and summarize the available studies on the relationships among risk characteristics, alcohol involvement and brain development during this period. The cross-sectional designs and small samples characterizing available studies hamper definitive conclusions. This article will describe some of the opportunities contemporary neuroimaging techniques offer for advancing understanding of adolescent neurodevelopment and alcohol involvement.

Adolescents at risk for substance use disorders: role of psychological dysregulation, endophenotypes, and environmental influences.

Adolescents with alcohol-related problems often also use cigarettes and marijuana. Furthermore, early childhood characteristics that increase the risk for adolescent alcohol use disorders also increase the risk for problematic drug use. Identifying these characteristics early in childhood can be important for the prevention of alcohol and other drug (AOD) use disorders. As a result, researchers are seeking to identify liability factors and observable characteristics (i.e., phenotypes) that can predict substance use disorders (SUDs) across drug categories. Other studies are focusing on endophenotypes--characteristics that cannot be openly observed but which link a person's genetic makeup, or genotype, and disease. Both predictive behavioral phenotypes and endophenotypes may reveal pathways connecting heritable predispositions and early environmental influences to later SUDs. One suggested predictive phenotype is psychological dysregulation, which is characterized by cognitive, behavioral, and emotional difficulties in childhood. An endophenotype that has been studied extensively is a particular brain wave called the P300 event-related potential. For people who are at high risk of AOD use based on these characteristics, adverse environmental conditions frequently lead to SUDs. Given the strong evidence that childhood psychological dysregulation predicts problematic AOD use, effective interventions for preventing adolescent SUDs may need to target the environmental features that put adolescents with this behavioral constellation at increased risk.

Cardiovascular risk factors in adolescents with alcohol use disorders.

Among adults, chronic alcohol dependence is associated with cardiovascular disease (CVD). While it is unlikely that adolescents with alcohol use disorders (AUDs) would exhibit CVD, they might show elevated CVD risk factors. The purpose of this study was to compare CVD risk factors in adolescents with AUDs and an adolescent reference group. Adolescents with AUDs were recruited from treatment sources and reference adolescents were recruited from the community. Information about smoking behavior, exercise, and diet were gathered from interview and self-report measures. Body mass index and blood pressure were determined by physical exam and a blood sample was drawn to measure serum cholesterol and triglycerides. Compared with the reference group, adolescents with AUDs reported significantly more smoking, were less likely to report exercising regularly, and were less likely to report eating a balanced diet. Adolescents with AUDs were not more likely to be overweight or to exhibit hypertension, and lipid levels were also not significantly elevated. These results indicated that adolescents with AUDs endorsed problematic health behaviors while not yet exhibiting the consequences of these behaviors. Interventions focusing on health behaviors in conjunction with addiction treatment might help improve long-term health outcomes in adolescents with AUDs.

Prefrontal cortex, thalamus, and cerebellar volumes in adolescents and young adults with adolescent-onset alcohol use disorders and comorbid mental disorders.

BACKGROUND: In adults, prefrontal, thalamic, and cerebellar brain injury is associated with excessive ethanol intake. As these brain structures are actively maturing during adolescence, we hypothesized that subjects with adolescent-onset alcohol use disorders, compared with control subjects, would have smaller brain volumes in these areas. Thus, we compared prefrontal-thalamic-cerebellar measures of adolescents and young adults with adolescent-onset alcohol use disorders (AUD, defined as DSM-IV alcohol dependence or abuse) with those of sociodemographically similar control subjects. METHODS: Magnetic resonance imaging was used to measure prefrontal cortex, thalamic, and cerebellar volumes in 14 subjects (eight males, six females) with an AUD (mean age, 17.0+/-2.1 years) and 28 control subjects (16 males, 12 females; 16.9+/-2.3 years). All AUD subjects were recruited from substance abuse treatment programs and had comorbid mental disorders. RESULTS: Subjects with alcohol use disorders had smaller prefrontal cortex and prefrontal cortex white matter volumes compared with control subjects. Right, left, and total thalamic, pons/brainstem, right and left cerebellar hemispheric, total cerebellar, and cerebellar vermis volumes did not differ between groups. There was a significant sex-by-group effect, indicating that males with an adolescent-onset AUD compared with control males had smaller cerebellar volumes, whereas the two female groups did not differ in cerebellar volumes. Prefrontal cortex volume variables significantly correlated with measures of alcohol consumption. CONCLUSIONS: These findings suggest that a smaller prefrontal cortex is associated with early-onset drinking in individuals with comorbid mental disorders. Further studies are warranted to examine if a smaller prefrontal cortex represents a vulnerability to, or a consequence of, early-onset drinking.

Exploratory factor analysis of two measures of posttraumatic stress disorder (PTSD) symptoms in a non-clinical sample of college students.

This study investigated the psychometric structure of two widely utilized measures of posttraumatic symptoms in a primarily Caucasian non-clinical sample. Given the prevalence of trauma exposure in non-referred samples, measurement of resulting symptoms is a critical issue. Exploratory factor analysis was utilized to assess and compare the factor structure of the Impact of Event Scale [IES; Horowitz, M., Wilner, N., & Alvarez, W. (1979). Impact of Event Scale: a measure of subjective stress. Psychosomatic Medicine, 41, 209-218] and the Mississippi Scale for Posttraumatic Stress Disorder, Civilian version [MIS-Civ; Vreven, D. L., Gudanowski, D. M., King, L. A., & King, D. W. (1995). The Civilian Version of the Mississippi PTSD Scale-a psychometric evaluation. Journal of Traumatic Stress, 8, 91-109] in a sample of college students reporting exposure to potentially traumatic events. The psychometric structure of the IES was largely consistent with the two-factor structure widely reported in the literature, while the structure of the MIS-Civ varied considerably in this sample. Notably, non-clinical samples tended to report fewer social and occupational dysfunction than clinical samples predominantly utilized in PTSD research. Implications for use of these instruments in screening samples are discussed.

Supervisory neglect and adolescent alcohol use disorders: effects on AUD onset and treatment outcome.

BACKGROUND: While parental supervision has been demonstrated to influence adolescent alcohol involvement, lack of a threshold defining inadequate supervision and little study of DSM defined alcohol use disorders (AUDs) have limited clinical applications. Utilizing a four-item supervision scale, this study identified adolescents with inadequate supervision, and examined effects on AUD development and treatment outcome. METHODS: Two groups of adolescent subjects (ages 14-17) were recruited: (1) a representative community sample of adolescents (n = 170) and (2) adolescents with AUDs from drug and alcohol or psychiatric treatment programs (n = 194). Supervision was determined by the adolescent's responses to items inquiring whether parents typically had knowledge of the adolescent's activities away from home, including with whom, where, when, and communication items. Adolescents with unusually low parental supervision (i.e., Supervisory Neglect) were identified by scale distributions. Follow-up assessments were conducted 1, 3, and 5 years after the initial assessment. RESULTS: Among community subjects, adolescents with inadequate supervision were significantly more likely to drink alcohol in a variety of situations, were more likely to have AUDs at the initial assessment and, among those without AUDs, were more likely to develop AUDs in the follow-up period. Among adolescents receiving treatment for AUDs, those with inadequate supervision were less likely to be free of AUD symptoms over a 1-year follow-up period. CONCLUSIONS: These results indicate that the described method was a straightforward and potentially clinically applicable approach to identifying adolescents with inadequate parental supervision.

Adolescent alcohol use disorders predict adult borderline personality.

BACKGROUND: This study investigated adolescent alcohol use disorders (AUDs) and other characteristics as predictors of adult borderline personality disorder (BPD) symptoms. METHODS: Adolescents with AUDs (n = 355) were recruited from clinical treatment sources and adolescents without AUDs (n = 169) were recruited from the community. During an adolescent assessment (age 16+/-1.3), childhood physical and/or sexual abuse history, AUDs and associated psychiatric disorders were measured via semi-structured interviews. Symptoms of BPD were measured in a young adult follow-up assessment (age 22+/-2.4). Latent class analysis was utilized to classify individuals into four categories based upon BPD symptom profiles. RESULTS: Multinomial regression models indicated that adolescent AUDs and other psychiatric disorders mediated the relationship between child physical and/or sexual abuse and adult BPD latent class. CONCLUSIONS: Results were consistent with a developmental conceptualization of BPD, with AUDs and other adolescent psychopathology antecedents representing developmentally relevant forms of dysregulation, and in their more severe forms culminating in borderline symptomatology.

Adolescent neglect and alcohol use disorders in two-parent families.

Parental responsibilities to adolescents include supervision and emotional support, and variations in these parenting behaviors have been demonstrated to influence adolescent alcohol involvement. This study developed a scale-based method for identifying adolescents with low-parent involvement and examined effects on the development and course of alcohol use disorders (AUDs). The participants were 361 adolescents (ages 14 to 17 years) from two-parent families recruited from clinical and community sources. Cluster analysis of questionnaire items describing mother and father involvement identified 75 adolescents with low-parent involvement (i.e., Neglect). Compared with reference adolescents, Neglect adolescents were significantly more likely to be influenced by social pressure to drink alcohol. Among community participants, Neglect adolescents were more likely to develop AUDs. Among adolescents receiving treatment for AUDs, those in the Neglect group showed more improvement during a 1-year follow-up period. The results indicate that inadequate parent involvement may be a form of neglect.