Duncan B. Clark

Developmental traumatology part II : Brain development

Abstract Background: Previous investigations suggest that maltreated children with a diagnosis of posttraumatic stress disorder (PTSD) evidence alterations of biological stress systems. Increased levels of catecholaminergic neurotransmitters and steroid hormones during traumatic experiences in childhood could conceivably adversely affect brain development. Methods: In this study, 44 maltreated children and adolescents with PTSD and 61 matched controls underwent comprehensive psychiatric and neuropsychological assessments and an anatomical magnetic resonance imaging (MRI) brain scan. Results: PTSD subjects had smaller intracranial and cerebral volumes than matched controls. The total midsagittal area of corpus callosum and middle and posterior regions remained smaller; while right, left, and total lateral ventricles were proportionally larger than controls, after adjustment for intracranial volume. Brain volume robustly and positively correlated with age of onset of PTSD trauma and negatively correlated with duration of abuse. Symptoms of intrusive thoughts, avoidance, hyperarousal or dissociation correlated positively with ventricular volume, and negatively with brain volume and total corpus callosum and regional measures. Significant gender by diagnosis effect revealed greater corpus callosum area reduction in maltreated males with PTSD and a trend for greater cerebral volume reduction than maltreated females with PTSD. The predicted decrease in hippocampal volume seen in adult PTSD was not seen in these subjects. Conclusions: These data suggest that the overwhelming stress of maltreatment experiences in childhood is associated with adverse brain development.

Is there an association between alcohol consumption and sexually transmitted diseases? A systematic review.

Objective/Goal: The objective of this study was to conduct a systematic review of published literature on the association between problematic alcohol consumption and sexually transmitted diseases (STDs). Design: Using a MEDLINE search (1995–2003) and article references, we identified articles that described measures of alcohol consumption and STDs and presented data on their association. For each eligible study, we classified the alcohol consumption measure as specific (problem drinking) or general, and examined study designs, study populations, STD measures, and results. Results: Of 42 eligible studies, 11 included specific measures of problem drinking, of which 8 found a significant association between alcohol consumption and at least 1 STD. The relationship did not appear to vary according to gender or pattern of alcohol consumption assessed. Conclusions: The literature supports an overall association between problematic alcohol consumption and STDs, although their causal relationship cannot be determined with certainty from these observational studies. The findings have implications for prevention planners, clinicians, and individual patients at risk of STDs.

Fluoxetine for the Treatment of Childhood Anxiety Disorders

OBJECTIVE To assess the efficacy and tolerability of fluoxetine for the acute treatment of children and adolescents with generalized anxiety disorder, separation anxiety disorder, and/or social phobia. METHOD Anxious youths (7-17 years old) who had significant functional impairment were randomized to fluoxetine (20 mg/day) (n = 37) or placebo (n = 37) for 12 weeks. RESULTS Fluoxetine was effective in reducing the anxiety symptoms and improving functioning in all measures. Using intent-to-treat analysis, 61% of patients taking fluoxetine and 35% taking placebo showed much to very much improvement. Despite this improvement, a substantial group of patients remained symptomatic. Fluoxetine was well tolerated except for mild and transient headaches and gastrointestinal side effects. Youths with social phobia and generalized anxiety disorder responded better to fluoxetine than placebo, but only social phobia moderated the clinical and functional response. Severity of the anxiety at intake and positive family history for anxiety predicted poorer functioning at the end of the study. CONCLUSIONS Fluoxetine is useful and well tolerated for the acute treatment of anxious youths. Investigations regarding the optimization of treatment to obtain full anxiety remission and the length of treatment necessary to prevent recurrences are warranted.

A.E. Bennett Research Award. Developmental traumatology. Part II: Brain development.

Abstract Background: Previous investigations suggest that maltreated children with a diagnosis of posttraumatic stress disorder (PTSD) evidence alterations of biological stress systems. Increased levels of catecholaminergic neurotransmitters and steroid hormones during traumatic experiences in childhood could conceivably adversely affect brain development. Methods: In this study, 44 maltreated children and adolescents with PTSD and 61 matched controls underwent comprehensive psychiatric and neuropsychological assessments and an anatomical magnetic resonance imaging (MRI) brain scan. Results: PTSD subjects had smaller intracranial and cerebral volumes than matched controls. The total midsagittal area of corpus callosum and middle and posterior regions remained smaller; while right, left, and total lateral ventricles were proportionally larger than controls, after adjustment for intracranial volume. Brain volume robustly and positively correlated with age of onset of PTSD trauma and negatively correlated with duration of abuse. Symptoms of intrusive thoughts, avoidance, hyperarousal or dissociation correlated positively with ventricular volume, and negatively with brain volume and total corpus callosum and regional measures. Significant gender by diagnosis effect revealed greater corpus callosum area reduction in maltreated males with PTSD and a trend for greater cerebral volume reduction than maltreated females with PTSD. The predicted decrease in hippocampal volume seen in adult PTSD was not seen in these subjects. Conclusions: These data suggest that the overwhelming stress of maltreatment experiences in childhood is associated with adverse brain development.

Gender and Comorbid Psychopathology in Adolescents With Alcohol Dependence

OBJECTIVE Although several mental disorders have been shown to be common in adolescents with substance use disorders, prior studies have not specifically focused on alcohol dependence and have not had sufficient sample sizes to examine gender effects. This study contrasts mental disorder diagnoses and symptoms between a sample of adolescents with alcohol dependence and a community control sample of adolescents and incorporates gender analyses. METHOD Adolescents (aged 14 years 0 months to 18 years 0 months) with alcohol dependence (females: n = 55; males: n = 78) and community-dwelling control adolescents without substance use disorders (females: n = 44; males: n = 42) were assessed by means of a semistructured interview for DSM-III-R. RESULTS While cannabis and hallucinogen use disorders were common in the alcohol dependence group, females and males had similar rates. Conduct disorder (CD), oppositional defiant disorder, attention-deficit hyperactivity disorder, major depression (MD), and posttraumatic stress disorder (PTSD) had significantly higher rates in the alcohol dependence than in the community control group. Depression and PTSD symptoms were more strongly associated with alcohol dependence in females than in males. A configural frequency analysis showed that CD and MD tended to occur together in both female and male adolescents with alcohol dependence. CONCLUSIONS While alcohol-dependent females and males similarly exhibited more comorbid disorders than control adolescents, gender affects the relationship of alcohol dependence to MD and PTSD. Rather than reflecting distinct types, the comorbid disorders of CD and MD jointly characterize many adolescents with alcohol dependence.

Traumas and Other Adverse Life Events in Adolescents With Alcohol Abuse and Dependence

OBJECTIVE Clinical observation suggests that adolescents with alcohol use disorders often have complex histories that include childhood maltreatment and other traumas. The aim of this study was to determine the relationships among adolescent alcohol use disorders and a broad range of traumas and adverse life events. METHOD The subjects were 132 adolescents with alcohol dependence, 51 adolescents with alcohol abuse, and 73 adolescents recruited from the community as a control group. Trauma history was assessed by a semistructured interview and other adverse life events by questionnaire. RESULTS Traumatic events reflecting interpersonal violence had occurred in many of the adolescents with alcohol dependence and abuse and few of the control adolescents. Adolescents with alcohol abuse or dependence, compared with control subjects, were 6 to 12 times more likely to have a physical abuse history and 18 to 21 times more likely to have a sexual abuse history. Sexual abuse was more common in females, and victimization by other violent acts was more common in males. Many other adverse life events were also significantly more common in the alcohol use disorder groups than in the control group, including having a close friend die, arguments within the family, and legal difficulties. CONCLUSIONS These results demonstrate that trauma and other adverse life events are strongly associated with alcohol use disorders in adolescents. Clinical screening of adolescents with alcohol use disorders for a range of traumatic events is recommended.

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.

Adolescent versus adult onset and the development of substance use disorders in males.

This study examines the influence of adolescent age of onset on the development of substance use disorders (SUD) by comparing adult males (n = 181) with SUD categorized into adolescent-onset, early-adult onset and late-adult onset groups on patterns of substance use and related disorders, time course of the development of substance dependence and rates of comorbid mental disorders. A sample of male adolescents (n = 81) with SUD was also included as a comparison group. The subjects were recruited from intervention programs in the community and participated in semistructured interviews with diagnoses determined by the best estimate method. Adolescent-onset adults, compared with other adult-onset groups, had higher lifetime rates of cannabis and hallucinogen use disorders, shorter times from first exposure to dependence, shorter times between the development of their first and second dependence diagnoses and higher rates of disruptive behavior disorders and major depression. Adolescents were similar to adolescent-onset adults. While the findings must be interpreted in light of methodological limitations, these results suggest that adolescent-onset SUD is a distinct subtype involving different substances and more rapid development than adult-onset SUD.

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.

Measuring risks and outcomes in substance use disorders prevention research.

Assessment planning in substance use disorder prevention research entails the identification of measurement domains and the selection of corresponding instruments needed to fulfill specific project goals. The study design, developmental periods examined, feasibility constraints, and anticipated statistical analyses are important considerations in optimally designing the assessment protocol. As a conceptual framework to organize the domains considered here as examples, the multifactorial model of complex disorders with elaborations emphasized by the discipline of developmental psychopathology is applied. Risks reviewed include family history, childhood maltreatment, peer relationships, and psychopathology. The substance involvement dimensions germane as outcomes include substance type, consumption quantity and frequency, and substance-related problems. Comprehensive diachronic evaluation over critical developmental periods provides the technical foundation for etiology and intervention research.