Sandra A. Brown

Reduction of immune function in life stress and depression

Reduced cell-mediated immune function has been found in depressed patients and in distressed persons undergoing threatening life events. The present study examines the interaction between severe life stress and major depression to produce immune alterations in 36 matched pairs of hospitalized depressed patients and nondepressed controls. Both major depressive disorder and the presence of threatening life events in control subjects are independently associated with a 50% reduction of natural killer (NK) cytotoxicity. A decrease in natural cytotoxicity is significantly associated with depressive symptoms but not with age, alcohol consumption, or tobacco smoking. These findings of altered immunity provide further evidence that the physiological responses in chronic stress parallel those found in the syndrome of depression.

Characteristics of relapse following adolescent substance abuse treatment

Historically research has focused on the characteristics of adults who relapse following treatment for alcohol or drug dependence. The circumstances of adolescent relapse, however, have largely gone unattended. The present study investigated the relapse rates and characteristics of adolescent posttreatment drug relapse. Seventy-five teens and their parents were interviewed while participating in an adolescent chemical dependency treatment program and at three and six months following treatment. Results indicate that a number of characteristics of adolescent relapse, including rates, are comparable to those of adults. In contrast to adult relapse, adolescent relapses occur most commonly in the presence of social pressure to drink. Situational characteristics of initial relapse experiences were different for transient or minor relapses and adolescent relapses which lead to a return to abusive drinking and drug use patterns.

Cognitive and behavioral features of adolescent coping in high-risk drinking situations

The present study examined the coping responses used by adolescents in high-risk situations. Sixty-six adolescents described situations in which it was difficult to resist drinking alcohol. Cognitive and behavioral responses in the perceived high-risk alcohol situations were examined. Abusing and nonabusing adolescents reported similar high-risk situations, but differed significantly in the cognitive and behavioral strategies used to cope with drinking pressures. Cognitive strategies associated with abstaining from alcohol use included defining oneself as a nondrinker and viewing other drinkers negatively. Behavioral responses associated with not drinking included engaging in an alternative activity and avoiding or limiting direct exposure to the high-risk situations. Theoretical and clinical implications for effective coping in alcohol situations are discussed.

Outcomes of Alcohol Treatment for Adolescents

The use by adolescents and young adults of alcohol and other drugs continues to be a tremendous problem for this nation. Over 30% of all high school students nationwide report episodes of hazardous drinking (five or more drinks on one occasion), when both moderate and heavy alcohol consumption are associated with a higher risk of alcohol-related medical consequences and accidental injuries for youth. Increased awareness and concern related to adolescent substance use has led to the outgrowth of additional treatment facilities and programs for this age group. The current chapter discusses how developmental factors may impact the assessment process and subsequent treatment for adolescent alcohol use disorders. In addition, outcome research, intervention studies, relapse, and factors that may influence the recovery process are discussed.

Psychiatric Comorbidity Among Inpatient Substance Abusing Adolescents

ABSTRACT We studied the association between type, severity and sequencing of psychopathology and these same dimensions of substance involvement among inpatient substance-abusing adolescents with comorbid psychiatric disorders. Adolescents (N = 140, 54% female; 15.9 years) meeting DSM-III-R criteria for a substance use disorder and at least one other Axis I psychiatric disorder were interviewed while inpatients in an adolescent psychiatric facility. Findings point to associations between externalizing disorders and a history of regular use of cigarettes, alcohol, and stimulants among comorbid adolescents. When sequencing of psychopathology was examined, different substance use patterns were observed. Severity of depressive disorders was associated with more substance withdrawal symptoms, externalizing symptomatology was related to more substance dependence symptoms, and ADHD severity was associated with more alcohol dependence symptoms. Findings may have important clinical implications such as the need to assess comorbidity early and to develop treatment plans based on type of comorbid psychiatric disorder.

Examination of genetic variation in GABRA2 with conduct disorder and alcohol abuse and dependence in a longitudinal study.

Previous studies have shown associations between single nucleotide polymorphisms (SNPs) in gamma aminobutyric acid receptor alpha 2 (GABRA2) and adolescent conduct disorder (CD) and alcohol dependence in adulthood, but not adolescent alcohol dependence. The present study was intended as a replication and extension of this work, focusing on adolescent CD, adolescent alcohol abuse and dependence (AAD), and adult AAD. Family based association tests were run using Hispanics and non-Hispanic European American subjects from two independent longitudinal samples. Although the analysis provided nominal support for an association with rs9291283 and AAD in adulthood and CD in adolescence, the current study failed to replicate previous associations between two well replicated GABRA2 SNPs and CD and alcohol dependence. Overall, these results emphasize the utility of including an independent replication sample in the study design, so that the results from an individual sample can be weighted in the context of its reproducibility.

Influences of Age, Sex, and Moderate Alcohol Drinking on the Intrinsic Functional Architecture of Adolescent Brains

The transition from adolescent to adult cognition and emotional control requires neurodevelopmental maturation likely involving intrinsic functional networks (IFNs). Normal neurodevelopment may be vulnerable to disruption from environmental insult such as alcohol consumption commonly initiated during adolescence. To test potential disruption to IFN maturation, we used resting-state functional magnetic resonance imaging (rs-fMRI) in 581 no-to-low alcohol-consuming and 117 moderate-to-high-drinking youth. Functional seed-to-voxel connectivity analysis assessed age, sex, and moderate alcohol drinking on default-mode, executive-control, salience, reward, and emotion networks and tested cognitive and motor coordination correlates of network connectivity. Among no-to-low alcohol-consuming adolescents, executive-control frontolimbicstriatal connectivity was stronger in older than younger adolescents, particularly boys, and predicted better ability in balance, memory, and impulse control. Connectivity patterns in moderate-to-high-drinking youth were tested mainly in late adolescence when drinking was initiated. Implicated was the emotion network with attenuated connectivity to default-mode network regions. Our cross-sectional rs-fMRI findings from this large cohort of adolescents show sexual dimorphism in connectivity and suggest neurodevelopmental rewiring toward stronger and spatially more distributed executive-control networking in older than younger adolescents. Functional network rewiring in moderate-to-high-drinking adolescents may impede maturation of affective and self-reflection systems and obscure maturation of complex social and emotional behaviors.

Altered Brain Developmental Trajectories in Adolescents After Initiating Drinking

OBJECTIVEnThe authors sought evidence for altered adolescent brain growth trajectory associated with moderate and heavy alcohol use in a large national, multisite, prospective study of adolescents before and after initiation of appreciable alcohol use.nnnMETHODnThis study examined 483 adolescents (ages 12-21) before initiation of drinking and 1 and 2 years later. At the 2-year assessment, 356 participants continued to meet the studys no/low alcohol consumption entry criteria, 65 had initiated moderate drinking, and 62 had initiated heavy drinking. MRI was used to quantify regional cortical and white matter volumes. Percent change per year (slopes) in adolescents who continued to meet no/low criteria served as developmental control trajectories against which to compare those who initiated moderate or heavy drinking.nnnRESULTSnIn no/low drinkers, gray matter volume declined throughout adolescence and slowed in many regions in later adolescence. Complementing gray matter declines, white matter regions grew at faster rates at younger ages and slowed toward young adulthood. Youths who initiated heavy drinking exhibited an accelerated frontal cortical gray matter trajectory, divergent from the norm. Although significant effects on trajectories were not observed in moderate drinkers, their intermediate position between no/low and heavy drinkers suggests a dose effect. Neither marijuana co-use nor baseline volumes contributed significantly to the alcohol effect.nnnCONCLUSIONSnInitiation of drinking during adolescence, with or without marijuana co-use, disordered normal brain growth trajectories. Factors possibly contributing to abnormal cortical volume trajectories include peak consumption in the past year and family history of alcoholism.

Bivariate Trajectories of Substance Use and Antisocial Behavior Associations With Emerging Adult Outcomes in a High-Risk Sample

Substance use and antisocial behavior (ASB) are complex and interrelated behaviors. This study identified model trajectory classes defined by concurrent substance use and ASB and examined trajectory associations with emerging adult outcomes. Participants from a high-risk sample of youth (n = 536; 73% male) completed interviews at baseline (mean age = 16.1 years) and follow-up (mean age = 22.6 years). Latent class growth analyses identified five trajectory classes based on alcohol/drug use (AOD) and ASB, namely, dual chronic, increasing AOD/persistent ASB, persistent AOD/adolescent ASB, decreasing drugs/persistent ASB, and resolved. Many individuals (56%) exhibited elevated/increasing AOD, and most (91%) reported ASB decreases. Those associated with the dual chronic class had the highest rates of substance dependence, antisocial personality disorder, and negative psychosocial outcomes. There were no differences in adult role attainment across classes. Conjoint examination of these behaviors provides greater detail regarding clinical course and can inform secondary prevention and intervention efforts.

Structural brain anomalies in healthy adolescents in the NCANDA cohort: relation to neuropsychological test performance, sex, and ethnicity

Structural MRI of volunteers deemed “normal” following clinical interview provides a window into normal brain developmental morphology but also reveals unexpected dysmorphology, commonly known as “incidental findings.” Although unanticipated, these anatomical findings raise questions regarding possible treatment that could even ultimately require neurosurgical intervention, which itself carries significant risk but may not be indicated if the anomaly is nonprogressive or of no functional consequence. Neuroradiological readings of 833 structural MRI from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) cohort found an 11.8xa0% incidence of brain structural anomalies, represented proportionately across the five collection sites and ethnic groups. Anomalies included 26xa0mega cisterna magna, 15 subarachnoid cysts, 12 pineal cysts, 12 white matter dysmorphologies, 5 tonsillar ectopias, 5 prominent perivascular spaces, 5xa0gray matter heterotopias, 4 pituitary masses, 4 excessively large or asymmetrical ventricles, 4 cavum septum pellucidum, 3 developmental venous anomalies, 1 exceptionally large midsagittal vein, and single cases requiring clinical followup: cranio-cervical junction stenosis, parietal cortical mass, and Chiari I malformation. A case of possible demyelinating disorder (e.g., neuromyelitis optica or multiple sclerosis) newly emerged at the 1-year NCANDA followup, requiring clinical referral. Comparing test performance of the 98 anomalous cases with 619 anomaly-free no-to-low alcohol consuming adolescents revealed significantly lower scores on speed measures of attention and motor functions; these differences were not attributed to any one anomaly subgroup. Further, we devised an automated approach for quantifying posterior fossa CSF volumes for detection of mega cisterna magna, which represented 26.5xa0% of clinically identified anomalies. Automated quantification fit a Gaussian distribution with a rightward skew. Using a 3SD cut-off, quantification identified 22 of the 26 clinically-identified cases, indicating that cases with percent of CSF in the posterior-inferior-middle aspect of the posterior fossa ≥3SD merit further review, and support complementing clinical readings with objective quantitative analysis. Discovery of asymptomatic brain structural anomalies, even when no clinical action is indicated, can be disconcerting to the individual and responsible family members, raising a disclosure dilemma: refrain from relating the incidental findings to avoid unnecessary alarm or anxiety; or alternatively, relate the neuroradiological findings as “normal variants” to the study volunteers and family, thereby equipping them with knowledge for the future should they have the occasion for a brain scan following an illness or accident that the incidental findings predated the later event.