Borderline personality disorder symptoms in treatment-naïve actively drinking alcoholics.

Borderline personality disorder (BPD) is often a complicating comorbid factor in alcohol use disorders and substance use disorders. Previous work showed that abstinent alcoholics endorsed lifetime and current symptoms of most of the BPD criteria at much higher rates than controls, with much higher symptom counts for short-term abstinent alcoholic (STAA) women than men, which is consistent with such symptoms negatively affecting female alcoholics' ability to maintain abstinence. Because prior work has also shown that treatment-naïve alcoholics (TNA) are not the same as treated alcoholics observed earlier in their alcohol dependence, but rather are a different population with potentially lower psychiatric comorbidity, in this study we compared BPD symptom criteria between TNA samples of comparable age to the control and STAA samples, including both men and women and individuals dependent on alcohol only or with lifetime dependence on both alcohol and drugs.

EEG coherence related to fMRI resting state synchrony in long-term abstinent alcoholics.

Recent work suggests that faulty co-activation or synchrony of multiple brain regions comprising "networks," or an imbalance between opposing brain networks, is important in alcoholism. Previous studies showed higher fMRI resting state synchrony (RSS) within the executive control (inhibitory control and emotion regulation) networks and lower RSS within the appetitive drive network in long-term (multi-year) abstinent alcoholics (LTAA) vs. non substance abusing controls (NSAC).

P3b amplitude is not reduced in abstinent alcoholics with a current MDD.

In two studies of long-term abstinent alcoholics (LTAAs), we found that about 17% had a current major depressive disorder (MDD). We tested the hypothesis that LTAAs with a current MDD diagnosis do not exhibit the reduced P3b event-related potential amplitude endophenotype for alcoholism. This is consistent with the majority of LTAAs with a current MDD having developed alcohol dependence via self-medication of their MDD rather than their alcohol dependence arising from the alcoholism endophenotype.

Resting state synchrony in long-term abstinent alcoholics: Effects of a current major depressive disorder diagnosis.

Alcoholism is characterized by a lack of control over an impulsive and compulsive drive toward excessive alcohol consumption despite significant negative consequences; our previous work demonstrated that successful abstinence is characterized by decreased resting-state synchrony (RSS) as measured with functional magnetic resonance imaging (fMRI), within appetitive drive networks and increased RSS in emotion regulation and inhibitory executive control networks. Our hypothesis is that LTAA (Long-Term Abstinent Alcoholics) with a current major depressive disorder (MDD) drank primarily to deal with the negative affect associated with their MDD and not because of a heightened externalizing diathesis (including heightened appetitive drive), and consequently, in achieving and maintaining abstinence, such individuals would not exhibit the RSS adaptations characteristic of pure alcoholics. We studied 69 NSAC (Non Substance Abusing Controls) and 40 LTAA (8 with current MDD, 32 without a current MDD) using resting-state fMRI and seed based connectivity analyses.

Genetic variation within GRIN2B in adolescents with alcohol use disorder may be associated with larger left posterior cingulate cortex volume.

Objective: Brain structure differences and adolescent alcohol dependence both show substantial heritability. However, exactly which genes are responsible for brain volume variation in adolescents with substance abuse disorders are currently unknown. The aim of this investigation was to determine whether genetic variants previously implicated in psychiatric disorders are associated with variation in brain volume in adolescents with alcohol use disorder (AUD).

Psychiatric Comorbidity in Alcohol Dependence.

We review our clinical studies of psychiatric comorbidity in short-term and long-term abstinent and in treatment naïve alcoholics (STAA, LTAA and TNA). TNA ypically have less severe alcoholism than treated abstinent samples and evidence less severe psychiatric disturbance. Lifetime psychiatric diagnoses are the norm for STAA and LTAA but not for TNA.

Possible involvement of the circadian pathway in alcohol use disorder in a South African adolescent cohort.

Alcoholism has an estimated heritability of between 40 and 60% and it is thought that several genes of small effect may contribute to the risk of developing this disorder. Studies of the genetics of alcohol use disorder (AUD) may, however, be confounded by issues of comorbidity. The aim of this investigation was to assess associations between variants in a range of candidate genes and AUD in a unique sample of adolescents without comorbidity.

Neuroplasticity in Human Alcoholism: Studies of Extended Abstinence with Potential Treatment Implications.

Alcoholism is characterized by a lack of control over excessive alcohol consumption despite significant negative consequences. This impulsive and compulsive behavior may be related to functional abnormalities within networks of brain regions responsible for how we make decisions. The abnormalities may result in strengthened networks related to appetitive drive-or the need to fulfill desires-and simultaneously weakened networks that exercise control over behaviors.

Brain pathways to recovery from alcohol dependence.

This article highlights the research presentations at the satellite symposium on "Brain Pathways to Recovery from Alcohol Dependence" held at the 2013 Society for Neuroscience Annual Meeting. The purpose of this symposium was to provide an up to date overview of research efforts focusing on understanding brain mechanisms that contribute to recovery from alcohol dependence. A panel of scientists from the alcohol and addiction research field presented their insights and perspectives on brain mechanisms that may underlie both recovery and lack of recovery from alcohol dependence.

The BDNF p.Val66Met polymorphism, childhood trauma, and brain volumes in adolescents with alcohol abuse.

Background: Previous studies have indicated that early life adversity, genetic factors and alcohol dependence are associated with reduced brain volume in adolescents. However, data on the interactive effects of early life adversity, genetic factors (e.g.

Decision making, risky behavior, and alcoholism.

Alcoholism can be described as a disorder characterized by impulsive decision-making processes, wherein potential short-term appetitive outcomes of drinking (e.g., intoxication) are deemed more important than potential long-term aversive consequences of drinking (e.

Automated MRI cerebellar size measurements using active appearance modeling.

Although the human cerebellum has been increasingly identified as an important hub that shows potential for helping in the diagnosis of a large spectrum of disorders, such as alcoholism, autism, and fetal alcohol spectrum disorder, the high costs associated with manual segmentation, and low availability of reliable automated cerebellar segmentation tools, has resulted in a limited focus on cerebellar measurement in human neuroimaging studies. We present here the CATK (Cerebellar Analysis Toolkit), which is based on the Bayesian framework implemented in FMRIB's FIRST. This approach involves training Active Appearance Models (AAMs) using hand-delineated examples.

Automated cerebellar segmentation: Validation and application to detect smaller volumes in children prenatally exposed to alcohol.

Objective: To validate an automated cerebellar segmentation method based on active shape and appearance modeling and then segment the cerebellum on images acquired from adolescents with histories of prenatal alcohol exposure (PAE) and non-exposed controls (NC).

Methods: Automated segmentations of the total cerebellum, right and left cerebellar hemispheres, and three vermal lobes (anterior, lobules I-V; superior posterior, lobules VI-VII; inferior posterior, lobules VIII-X) were compared to expert manual labelings on 20 subjects, studied twice, that were not used for model training. The method was also used to segment the cerebellum on 11 PAE and 9 NC adolescents.

Haplotype-based study of the association of alcohol and acetaldehyde-metabolising genes with alcohol dependence (with or without comorbid anxiety symptoms) in a Cape Mixed Ancestry population.

Alcohol dependence (AD) has a large heritable component. Genetic variation in genes involved in the absorption and elimination of ethanol have been associated with AD. However, some of these polymorphisms are not present in an African population.

The cross-cultural utility of foreign- and locally-derived normative data for three WHO-endorsed neuropsychological tests for South African adolescents.

Interpretation of neuropsychological tests may be hampered by confounding sociodemographic factors and by using inappropriate normative data. We investigated these factors in three tests endorsed by the World Health Organization: the Grooved Pegboard Test (GPT), the Children's Color Trails Test (CCTT), and the WHO/UCLA version of the Auditory Verbal Learning Test (AVLT). In a sample of 12-15-year-old, Afrikaans- and English-speaking adolescents from the Cape Town region of South Africa, analyses of covariance (ANCOVAs) demonstrated that quality of education was the sociodemographic factor with the biggest influence on test performance, and that age also significantly influenced GPT and CCTT performance.

Childhood adversity is linked to differential brain volumes in adolescents with alcohol use disorder: a voxel-based morphometry study.

Previous neuroimaging studies link both alcohol use disorder (AUD) and early adversity to neurobiological differences in the adult brain. However, the association between AUD and childhood adversity and effects on the developing adolescent brain are less clear, due in part to the confound of psychiatric comorbidity. Here we examine early life adversity and its association with brain volume in a unique sample of 116 South African adolescents (aged 12-16) with AUD but without psychiatric comorbidity.

Subcortical volumes are reduced in short-term and long-term abstinent alcoholics but not those with a comorbid stimulant disorder.

Chronic alcohol abuse affects brain structure and function. We examined subcortical structure volumes in 77 short (6-15 week) and 90 long (multi-year) term abstinent alcoholics, along with 74 controls. We used a 3T Siemens MPRAGE sequence for image acquisition and FSL FIRST software for measuring subcortical volumes.

Not lesser but Greater fractional anisotropy in adolescents with alcohol use disorders.

Objective: The objective of this study is to examine white matter microstructure using diffusion tensor imaging (DTI) in a sample of adolescents with alcohol use disorders (AUD) and no psychiatric or substance co-morbidity.

Methods: Fifty adolescents with AUD and fifty non-alcohol abusing controls matched on gender and age were studied with DTI, neurocognitive testing, and a clinical assessment that included measures of alcohol use and childhood trauma. Maps of fractional anisotropy (FA) and mean diffusivity (MD) were computed, registered to a common template, and voxel-wise statistical analysis used to assess group differences.

Cortical and subcortical volumes in adolescents with alcohol dependence but without substance or psychiatric comorbidities.

Most prior studies of the effects of excessive alcohol intake on the adolescent brain examined alcohol-use-dependent samples with comorbid psychiatric and substance use disorders. In the Cape Town region, we identified a sizeable cohort of adolescents with alcohol use disorders (AUD) without externalizing or other psychiatric disorders. We examined brain morphology in 64 such adolescents compared to age- and gender-matched healthy controls.

Lifetime and current mood and anxiety disorders in short-term and long-term abstinent alcoholics.

Background: A high prevalence of comorbid mood and anxiety disorders has been demonstrated in alcoholics. We examined lifetime and current mood and anxiety diagnoses and symptoms in long-term (mean 7.6 years; n = 110) and short-term (mean 10.

Resting state synchrony in long-term abstinent alcoholics with versus without comorbid drug dependence.

Background: We previously reported that when long-term abstinent alcoholics (LTAA; with no drug comorbidity) are compared to controls, they show increased resting state synchrony (RSS) in the executive control network and reduced RSS in the appetitive drive network suggestive of compensatory mechanisms that may facilitate abstinence. The aim of the present study was to investigate whether long-term abstinent alcoholics with comorbid stimulants dependence (LTAAS) show similar RSS mechanisms.

Methods: Resting-state functional MRI data were collected on 36 LTAAS (20 females, age: 47.

Resting-state synchrony in short-term versus long-term abstinent alcoholics.

Background: We previously reported that when compared with controls, long-term abstinent alcoholics (LTAA) have increased resting-state synchrony (RSS) of the inhibitory control network and reduced synchrony of the appetitive drive network, and hypothesized that these levels of synchrony are adaptive and support the behavioral changes required to maintain abstinence. In this study, we investigate whether these RSS patterns can be identified in short-term abstinent alcoholics (STAA).

Methods: Resting-state functional magnetic resonance imaging data were collected from 27 STAA, 23 LTAA, and 23 nonsubstance abusing controls (NSAC).

Emotion-word processing difficulties in abstinent alcoholics with and without lifetime externalizing disorders.

Background: Evidence suggests that abstinent alcoholics have difficulties processing a variety of emotion-laden stimuli, and some of these difficulties may not fully resolve with long-term abstinence. The current study examined whether emotion-word processing difficulties were present in long-term abstinent alcoholics (LTAA; 18+ months of sobriety) with and without a previously diagnosed externalizing (EXT; antisocial personality disorder and/or attention-deficit/hyperactivity disorder diagnosis) disorder.

Methods: Subjects (N = 121) completed an affective go/no-go (AGNG) task with positive, negative, and neutral emotion-word stimuli, and a lexical decision-making (LDM) task with nonemotion word and nonword stimuli.

Theta event-related synchronization is a biomarker for a morbid effect of alcoholism on the brain that may partially resolve with extended abstinence.

Analyzing the induced (non-stimulus-phase-locked) EEG activity elicited by targets in a three-condition visual oddball task, Fein and colleagues have shown increased theta band event-related synchronization (ERS) in two different samples of long-term abstinent alcoholics (LTAA) compared with age- and gender-comparable controls. The theta ERS effect in alcoholics was also shown to be independent of, and opposite in direction to, the reduced amplitude evoked (stimulus-phase-locked) activity typically found in alcoholics and those at genetic risk of developing alcoholism. This study extends these findings by applying time-frequency analysis to target stimulus event-related EEG to compare evoked and induced theta activity in 43 LTAA and 72 nonalcoholic controls with a group of 31 alcoholics who just recently initiated abstinence from alcohol (between 6- and 15-week abstinent; referred to as short-term abstinent alcoholics, STAA).