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). METHODS: The cohort consisted of 58 adolescents with DSM-IV AUD and 58 age and gender-matched controls of mixed ancestry ethnicity. An Illumina Infinium iSelect custom 6000 bead chip was used to genotype 5348 single nucleotide polymorphisms (SNPs) in 378 candidate genes. Magnetic resonance images were acquired and volumes of global and regional structures were estimated using voxel-based morphometry. To determine whether any of the genetic variants were associated with brain volume, association analysis was conducted using linear regression in Plink. RESULTS: From the exploratory analysis, the GRIN2B SNP rs219927 was associated with brain volume in the left posterior cingulate cortex (p<0.05), whereby having a G-allele was associated with a bigger volume. CONCLUSION: The GRIN2B gene is involved in glutamatergic signalling and may be associated with developmental differences in AUD in brain regions such as the posterior cingulate cortex. Such differences may play a role in risk for AUD, and deserve more detailed investigation.

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. Our cohort consisted of 80 adolescents with an AUD diagnosis and 80 matched controls of mixed ancestry ethnicity. An Illumina Infinium iSelect custom 6000 bead chip was used to genotype 5348 SNPs in 378 candidate genes. Association analysis, gene-based analysis and polygenic scoring were performed. There was no statistical association between any of the investigated SNPs and AUD after correction for multiple testing. However, from the gene-based analysis it was found that the circadian rhythm genes NR1D1 and BHLHE41 are associated with AUD. While preliminary, these data provide some evidence that the circadian pathway may be relevant to the pathophysiology of AUD. Study of early onset non-comorbid populations with AUD may be useful in identifying target genes for study in larger more representative samples.

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. Individuals with alcohol and drug use disorders show greater antisocial personality disturbance, but do not show differences in the mood or anxiety domains or in borderline personality disorder (BPD) symptoms. The studies show that alcoholics can achieve and maintain abstinence in the face of ongoing mood, anxiety, or BPD problems. By contrast, for ASPD, LTAA essentially stop current antisocial behaviors in all seven domains of antisocial behaviors. We believe that ongoing antisocial behavior is not consistent with maintaining abstinence, and that LTAA modify their antisocial behavior despite continued elevated social deviance proneness and antisocial dispositionality. Abstinent individuals without lifetime psychiatric disorders and TNA show more (subdiagnostic threshold) psychiatric symptoms and abnormal psychological measures than non-alcoholic controls in the mood, anxiety, BPD, and antisocial domains. In summary, our studies show that although LTAA have achieved multi-year abstinence, they still report significant psychological distress compared to NAC. We believe this distress may negatively affect their quality of life. This suggests the importance of developing effective care models to address comorbid mental health problems in LTAA. We also show that antisocial personality disorder symptoms decline to the levels seen in normal controls, and that excluding individuals from research with a psychiatric diagnosis does not control for subdiagnostic psychiatric differences between alcoholics and controls.

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. CATK can currently delineate the cerebellar hemispheres and three vermal groups (lobules I-V, VI-VII, and VIII-X). Linear registration with the low-resolution MNI152 template is used to provide initial alignment, and Point Distribution Models (PDM) are parameterized using stellar sampling. The Bayesian approach models the relationship between shape and texture through computation of conditionals in the training set. Our method varies from the FIRST framework in that initial fitting is driven by 1D intensity profile matching, and the conditional likelihood function is subsequently used to refine fitting. The method was developed using T1-weighted images from 63 subjects that were imaged and manually labeled: 43 subjects were scanned once and were used for training models, and 20 subjects were imaged twice (with manual labeling applied to both runs) and used to assess reliability and validity. Intraclass correlation analysis shows that CATK is highly reliable (average test-retest ICCs of 0.96), and offers excellent agreement with the gold standard (average validity ICC of 0.87 against manual labels). Comparisons against an alternative atlas-based approach, SUIT (Spatially Unbiased Infratentorial Template), that registers images with a high-resolution template of the cerebellum, show that our AAM approach offers superior reliability and validity. Extensions of CATK to cerebellar hemisphere parcels are envisioned.

Resting-state synchrony during early alcohol abstinence can predict subsequent relapse.

Short-term abstinent alcoholics have shown increased engagement of reward regions and reduced engagement of executive control regions. There is no report yet on whether these differences can predict relapse. This is the first study that investigates whether differences in resting-state networks can predict later relapse. Resting-state functional magnetic resonance imaging data were collected from 69 short-term abstinent alcoholics. Participants performed the affective go/no-go task outside of the scanner. At 6-month follow-up, participants were grouped as abstainers (N = 40; age: M = 46.70, standard deviation [SD] = 6.83) and relapsers (N = 29; age: M = 46.91, SD = 7.25). We examined baseline resting-state synchrony (RSS) using seed-based measures. Compared with abstainers, relapsers showed significantly decreased RSS within both the reward and executive control networks as well as within the visual network (P < 0.05). Lower RSS in relapsers could predict relapse (P < 0.05) and was significantly correlated with poor inhibitory control of emotional-laden stimuli (P < 0.017) and with alcohol use (P < 0.05). Results suggest that lower RSS during short-term abstinence may predict subsequent relapse. The association of lower RSS with poorer inhibitory control suggests that low RSS may constitute a faulty foundation for future responses to external cues, which can be manifested as the inability to inhibit behavior.

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. p.Met66 allele of BDNF), and alcohol dependence, on brain structure in adolescents is limited. We examined whether the BDNF p.Val66Met polymorphism interacts with childhood trauma to predict alterations in brain volume in adolescents with alcohol use disorders (AUDs). METHODS: We examined 160 participants (80 adolescents with DSM-IV AUD and 80 age- and gender-matched controls) who were assessed for trauma using the Childhood Trauma Questionnaire (CTQ). Magnetic resonance images were acquired for a subset of the cohort (58 AUD and 58 controls) and volumes of global and regional structures were estimated using voxel-based morphometry (VBM). Samples were genotyped for the p.Val66Met polymorphism using the TaqMan® Assay. Analysis of covariance (ANCOVA) and post-hoc t-tests were conducted using SPM8 VBM. RESULTS: No significant associations, corrected for multiple comparisons, were found between the BDNF p.Val66Met polymorphism, brain volumes and AUD in adolescents with childhood trauma. CONCLUSIONS: These preliminary findings suggest that the BDNF p.Met66 allele and childhood trauma may not be associated with reduced structural volumes in AUD. Other genetic contributors should be investigated in future studies.

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. Participants were 58 adolescents with DSM-IV alcohol dependence and with no other psychiatric comorbidities, and 58 age-, gender- and protocol-matched light/non-drinking controls (HC). Assessments included the Childhood Trauma Questionnaire (CTQ). MR images were acquired on a 3T Siemens Magnetom Allegra scanner. Volumes of global and regional structures were estimated using SPM8 Voxel Based Morphometry (VBM), with analysis of covariance (ANCOVA) and regression analyses. In whole brain ANCOVA analyses, a main effect of group when examining the AUD effect after covarying out CTQ was observed on brain volume in bilateral superior temporal gyrus. Subsequent regression analyses to examine how childhood trauma scores are linked to brain volumes in the total cohort revealed a negative correlation in the left hippocampus and right precentral gyrus. Furthermore, bilateral (but most significantly left) hippocampal volume was negatively associated with sub-scores on the CTQ in the total cohort. These findings support our view that some alterations found in brain volumes in studies of adolescent AUD may reflect the impact of confounding factors such as psychiatric comorbidity rather than the effects of alcohol per se. In particular, early life adversity may influence the developing adolescent brain in specific brain regions, such as the hippocampus.

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. Previous studies have reported that a type of AD which is characterized by anxious behaviour may be a genetically specific subtype of AD. We investigated whether variation in genes encoding cytochrome P450 2E1 (CYP2E1) or acetaldehyde-metabolising enzymes (ALDH1A1, ALDH2) might alter the risk of AD, with and without symptoms of anxiety, in a Cape population with mixed ancestry. Eighty case control pairs (one with AD, one without AD) were recruited and individually matched for potential confounders. Genotype data were available for 29 single-nucleotide polymorphisms (SNPs) across the three genes. Linkage disequilibrium D' values were evaluated for all pairwise comparisons. Allele and haplotype frequencies were compared between cases and controls using a χ2 test. The ACAG haplotype in block 4 of the ALDH1A1 gene provided evidence of an association with AD (p = 0.03) and weak evidence of an association with AD without symptoms of anxiety (p = 0.06). When a genetic score was constructed using SNPs showing nominal evidence of association with AD, every extra risk allele increased the odds of AD by 35% (OR 1.35, 95% CI 1.08, 1.68, p = 0.008) and the odds of having AD with anxiety symptoms increased by 53% (OR 1.53, 95% CI 1.14, 2.05, p = 0.004). Although our results are supported by previous studies in other populations, they must be interpreted with caution due to the small sample size and the potential influence of population stratification.

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. Based on those findings, we provide appropriately stratified normative data for the age group in question. Comparisons between diagnostic interpretations made using foreign normative data versus those using the current local data demonstrate that it is imperative to use appropriately stratified normative data to guard against misinterpreting performance.

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 10.1 weeks; n = 101) abstinent alcoholics (LTAA and STAA) and nonsubstance abusing controls (NSAC; n = 82). All alcoholics met DSM-IV lifetime alcohol dependence criteria. About half of each alcoholic group had lifetime drug dependence. METHODS: Alcohol use was assessed using timeline follow-back methodology, and drug and alcohol use disorders were diagnosed using the AUDADIS-IV. Lifetime and current mood and anxiety disorder diagnoses and symptom counts were gathered using the computerized Diagnostic Interview Schedule. RESULTS: Over 60% of STAA and LTAA had a lifetime internalizing diagnosis versus about 15% of NSAC, with no difference between STAA and LTAA. The group effect on lifetime diagnoses was independent of comorbid drug dependence or gender and was of comparable size for mood and anxiety disorders. Current diagnoses showed a similar pattern, except that STAA had more current mood diagnoses than LTAA. Excluding individuals with lifetime internalizing diagnoses, alcoholics still had more mood and anxiety symptoms than controls. CONCLUSIONS: (i) The presence of a lifetime mood or anxiety diagnosis or of a current anxiety diagnosis did not differ between STAA and LTAA, suggesting that such diagnoses do not impact one's ability to achieve or maintain abstinence. (ii) Prevalence of mood and anxiety diagnoses was unaffected by presence of a comorbid substance use disorder, and (iii) excluding individuals with a mood or anxiety diagnosis does not eliminate mood and anxiety symptom count differences between groups.

Gait and balance deficits in chronic alcoholics: no improvement from 10 weeks through 1 year abstinence.

BACKGROUND: Disturbed gait and balance are common and important sequelae of chronic alcoholism. We present longitudinal data on recovery of gait and balance in alcoholics 6 to 15 weeks abstinent at baseline assessment through follow-up assessment 4 to 16 months after baseline. METHODS: We performed a follow-up assessment (4 to 16 months after baseline) of gait and balance functioning in 37 short-term (6 to 15 weeks) abstinent alcoholics (STAA), 25 of whom remained abstinent through the follow-up period. Fourteen non-substance-abusing controls (NSAC) were also brought back for a follow-up assessment to examine practice effects. RESULTS: Alcoholics showed gait and balance impairment versus controls at both the initial and follow-up assessments, showing no improvement in gait and balance measures over the follow-up period. At follow-up, NSAC showed improvement on the Walk on Floor eyes closed measure, possibly representing a practice effect not present in STAA. CONCLUSIONS: This study finds no improvement from about 10 weeks to about 1 year of abstinence in chronic alcoholics. The study is silent with regard to gait and balance recovery that occurs prior to 10 weeks abstinence, and after the first year of abstinence. Other studies suggest some recovery of gait and balance prior to 10 weeks abstinence, and our recent cross-sectional study (Smith and Fein, 2011, Alcohol Clin Exp Res 35:2184-2192) suggests that significant additional recovery occurs in the ensuing years.

Antisocial symptoms decrease to normal levels in long-term abstinence.

BACKGROUND: We have previously shown highly elevated antisocial symptoms and measures of social deviance proneness and antisocial disposition in long-term abstinent alcohol dependence versus non-substance-abusing controls (NSAC). Current antisocial symptoms were reduced to subdiagnostic levels in long-term abstinence; however, the number of current symptoms was not measured beyond its being subdiagnostic. METHODS: Here we measured social deviance proneness, antisocial disposition, and both lifetime and current antisocial symptoms in short-term and long-term abstinent substance-dependent and NSAC samples. RESULTS: Lifetime antisocial symptoms (and diagnoses) and social deviance proneness and antisocial disposition were highly elevated in both short- and long-term abstinence, replicating earlier findings. Current antisocial symptoms were dramatically reduced in long-term versus short-term abstinent samples, close to levels in controls. In contrast, social deviance proneness and antisocial disposition remain highly elevated in long-term abstinence. CONCLUSIONS: These findings suggest that antisocial behavior is reduced in extended abstinence, despite continued elevated social deviance proneness an antisocial disposition. This suggests a top-down model in extended abstinence, whereby executive control inhibits deviance-prone tendencies.

Resting-state synchrony in long-term abstinent alcoholics.

BACKGROUND: Alcohol dependence is a disorder with an impulsive and compulsive "drive" toward alcohol consumption and an inability to inhibit alcohol consumption. Neuroimaging studies suggest that these behavioral components correspond to an increased involvement of regions that mediate appetitive drive and reduced involvement of regions that mediate executive control within top-down networks. Little is known, however, about whether these characteristics are present after long periods of abstinence. METHODS: Resting-state functional magnetic resonance imaging data were collected to examine resting-state synchrony (RSS) differences between 23 long-term abstinent alcoholics (LTAA; 8 women, age: M = 48.46, SD = 7.10), and 23 nonsubstance abusing controls (NSAC; 8 women, age: M = 47.99, SD = 6.70). Using seed-based measures, we examined RSS with the nucleus accumbens (NAcc) and the subgenual anterior cingulate cortex (sgACC). All participants were assessed with the intra/extradimensional set shift task outside of the scanner to explore the relationship between RSS and cognitive flexibility. RESULTS: Compared to NSAC, LTAA showed (i) decreased synchrony of limbic reward regions (e.g., caudate and thalamus) with both the anterior cingulate cortex seed and the NAcc seed and (ii) increased synchrony of executive control regions (e.g., dorsolateral prefrontal cortex) with both the NAcc seed and the sgACC seed. RSS differences were significantly correlated with task performance. CONCLUSIONS: The results are consistent with an interpretation of an ongoing compensatory mechanism in LTAA evident during rest, in which decision-making networks show reduced synchrony with appetitive drive regions and increased synchrony with inhibitory control regions. In addition, RSS differences were associated with cognitive flexibility. These resting-state findings indicate an adaptive mechanism present in long-term abstinence that may facilitate the behavioral control required to maintain abstinence.

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. Nonsubstance abusing controls (NSAC; n = 38, 50.0% women, mean age = 48 ± 7.8), LTAA with EXT (n = 32, 41% women, mean age = 47.1 ± 6.6), and LTAA without EXT (n = 51, 47% women, mean age = 49.7 ± 6.5) were compared between signal discriminability (d') and mean response times (RT) for correct responses (mcRT). RESULTS: In the LDM task, LTAA had lower (d') values and slower mcRT than NSAC. In the AGNG task, LTAA and NSAC did not differ in AGNG task mcRT. LTAA had lower (d') values than NSAC, and this effect was partially associated with group differences in LDM task (d') values. In LTAA, lower AGNG (d') values also were associated with an earlier age of first drink, greater lifetime alcohol use, and a history of EXT disorder. CONCLUSIONS: Our findings suggest that detecting the emotional content of words is impaired in LTAA, and this impairment is over and above LTAA's more general lexical processing difficulties. Results also suggest that specific emotion processing impairments in LTAA may be exacerbated by greater lifetime alcohol use burden and other comorbid EXT diagnoses.

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). We examined baseline RSS using seed-based measures. RESULTS: We found ordered RSS effects from NSAC to STAA and then to LTAA within both the appetitive drive and executive control networks: increasing RSS of the executive control network and decreasing RSS of the reward processing network. Finally, we found significant correlations between strength of RSS in these networks and (i) cognitive flexibility, and (ii) current antisocial behavior. CONCLUSIONS: Findings are consistent with an adaptive progression of RSS from short- to long-term abstinence, so that, compared with normal controls, the synchrony (i) within the reward network progressively decreases, and (ii) within the executive control network progressively increases.

Absence of P300 reduction in South African treatment-naïve adolescents with alcohol dependence.

BACKGROUND: Event-related potential studies show reduced P300 amplitudes in alcohol use disorders (AUDs). Alcohol exposure, genetic vulnerability to alcoholism, and comorbid psychopathology may contribute to this reduction. Most previous research has studied treated adult AUD samples, which have more severe alcoholism, a greater family history of AUDs, and more comorbidity than untreated samples. Untreated AUD samples tend to have little or no P300 amplitude reduction. We compared P300 between treatment-naïve alcohol-dependent (TNAD) adolescents with no diagnosable substance abuse or psychiatric comorbidity and nonsubstance-abusing control (NSAC) adolescents. METHODS: Individuals between the ages of 13 and 18 years were recruited into either TNAD (n = 45) or NSAC (n = 64) groups. Alcohol use variables, family history density of alcohol problems, and psychiatric symptom counts were assessed in a clinician-administered evaluation. EEGs were recorded during performance of a 3-condition visual target detection task. RESULTS: P300 amplitudes were of comparable size in TNAD adolescents and NSAC adolescents. Boys demonstrated larger P3a and P3b amplitudes than girls. Within TNAD, P3b amplitude was reduced in those who drank more frequently, and P3a latency was more prolonged in subjects with higher internalizing symptom counts. CONCLUSIONS: The P300 deficit was not present in TNAD adolescents without comorbidities. In comparison to results of reduced P300 in treated adolescent AUD samples, this finding likely reflects moderate alcohol exposure, lower genetic vulnerability to alcoholism, and lack of comorbidity in our sample. Further work is needed to determine the relative contributions of these factors to changes in the P300.

Borderline personality symptoms in short-term and long-term abstinent alcohol dependence.

BACKGROUND: Comorbidity of borderline personality disorder (BPD) and substance and alcohol use disorders (SUDs and AUDs) is very high. The literature suggests a negative synergy between BPD and SUDs, which may impact an individual's ability to achieve and maintain remission of either disorder in the face of the other. METHODS: We examined lifetime and current (past year) BPD symptom counts in 3 gender- and age-comparable groups: short-term abstinent alcoholics (STA, 6 to 15 weeks abstinent), long-term abstinent alcoholics (LTA, more than 18 months abstinent), and nonsubstance-abusing controls (NSAC). Abstinent individuals were recruited primarily from mutual-help recovery networks and about half had comorbid drug dependence. BPD symptoms were obtained using the Structured Clinical Interview for DSM-IV-TR Axis II Personality Disorders, followed up with questions regarding currency, but did not require that BPD symptoms represent persistent or pervasive behavior such as would meet criteria for BPD diagnosis. Thus, our study dealt only with BPD symptoms, not BPD diagnoses. RESULTS: Alcoholics had more lifetime and current symptoms for most all BPD criteria than NSAC. In general, STA and LTA did not differ in BPD symptoms, except for a group-by-gender effect for both lifetime and current anger-associated symptoms and for lifetime abandonment avoidance symptoms. For these cases, there were much higher symptom counts for STA women versus men, with comparable symptom counts for LTA women versus men. CONCLUSIONS: Our results suggest for the most part that BPD symptoms do not prevent the maintenance of recovery in AUD and SUD individuals who have established at least 6 weeks abstinence within the mutual-help recovery network-in fact the presence of BPD symptoms is the norm. However, we did find difficulty in establishing longer-term abstinence in women with anger-associated symptoms and abandonment avoidance symptoms.

Gait and balance in treatment-naïve active alcoholics with and without a lifetime drug codependence.

BACKGROUND: Disturbed gait and balance are among the most consistent sequelae of chronic alcoholism. However, although a majority of alcoholics have never sought treatment, most investigations showing ataxia in alcohol-dependent individuals have relied on samples drawn from treated populations. In addition, few studies have addressed the associations of codependence on other drugs with alcoholic gait and balance disturbance. METHODS: This study employed the Walk-a-Line Ataxia Battery (Fregly et al. Alcohol Clin Exp Res 1972;43:395-399) to assess gait and balance in treatment-naïve, actively drinking alcohol-dependent men and women (TNA; n = 69) who were dependent on alcohol only (ALC; n = 43), or who also had a lifetime drug dependence (ALC + DRG; n = 26; i.e., methamphetamine, cocaine, opiates, and/or marijuana), compared with nonsubstance abusing controls (NSAC; n = 74).We also examined associations between lifetime alcohol use and age with gait and balance measures. RESULTS: Our main findings were (i) no evidence of disturbed gait and balance in ALC versus NSAC and (ii) significantly disturbed gait and balance in ALC + DRG, relative to both NSAC and ALC, along with steeper age-associated decline in gait and balance performance in ALC versus ALC + DRG. CONCLUSIONS: Our results provide evidence consistent with previous studies that TNA (without a lifetime drug codependence) may represent a population that is different and less impaired (including in gait and balance) than treated alcoholics. Additionally, we provide evidence that ALC + DRG, with greater alcohol use and family drinking density than ALC, have an accelerated effect of age on gait and balance disturbance compared with both NSAC and ALC. The ALC + DRG group likely represents a subset of TNA with different characteristics than ALC.

Event-related potentials during visual target detection in treatment-naïve active alcoholics.

BACKGROUND: Reduced P3b event-related potentials (ERP) amplitude during visual target detection in alcoholics is a robust phenomenon. However, this finding is based primarily on samples of treated alcoholics, who comprise only about 25% of alcoholics. We studied visual target detection in a treatment-naïve alcohol-dependent sample (TNAD) versus age and gender comparable nonalcoholic controls (NAC) to investigate whether reduced P3 amplitudes generalize to TNAD. METHODS: EEGs were recorded from 74 TNAD and 63 age and gender comparable NAC during visual target detection. ANOVA was applied at midline electrodes to amplitudes and latencies of N2 and P3 ERP components during target and rare nontarget conditions. RESULTS: Treatment-naïve alcohol-dependent subjects had a modestly lower P3b amplitude (p=0.05) and a more robustly lower N2b amplitude (p=0.29). In the target condition, TNAD showed a significant reduction in P3b amplitude and a larger reduction in N2b amplitude, with these phenomena being independent of each other. Latencies to P3b, N2b, and P3a were earlier in TNAD than NAC, with this effect correlating with our reported effect of better attention in TNAD versus NAC. CONCLUSION: The significant reduction in P3b amplitude in TNAD suggests that this phenomenon is present in TNAD, but dramatically smaller than that observed in treated samples (we reported an effect over 5 times as large in treated long-term abstinent alcoholics). The N2b amplitude reduction (not present in long-term abstinent alcoholics) may reflect the effects of active alcohol abuse. Finally, the shorter latencies of these components in TNAD is associated with better scores on tests of attention and may reflect compensatory attentional effort in the context of active drinking.

Persistent but less severe ataxia in long-term versus short-term abstinent alcoholic men and women: a cross-sectional analysis.

BACKGROUND: Disturbed gait and balance are among the most consistent and salient sequelae of chronic alcoholism. Results of small sample longitudinal investigations have provided evidence that partial recovery of gait and balance functions in alcoholics may be achieved with abstinence. However, abstinence durations reported have been limited, and their power and generalizability have suffered from small sample sizes. METHODS: In this study, we employed a cross-sectional approach to assess gait and balance functions in short-term (6 to 15 weeks) abstinent alcoholics (STAA; n = 70) and long-term (minimum 18 months, mean = 7.38 years) abstinent alcoholics (LTAA; n = 82). STAA and LTAA did not differ with respect to lifetime alcohol consumption, family drinking density, or years of education. In addition, we examined the effects of gender and alcohol use variables. RESULTS: Our main findings were: (i) persistent disturbed gait and balance in STAA and disturbed standing balance in LTAA; (ii) overall less impaired performance of LTAA compared with STAA on gait and balance measures; and (iii) worse performance of STAA (but not LTAA) women, compared with men, on standing balance without visual control. CONCLUSIONS: Our results suggest that alcoholics' gait and balance can continue to recover with long abstinence from alcohol, but that deficits persist, especially in eyes-closed standing balance. In addition, our results are consistent with more severe alcohol-induced ataxia in women than in men but suggest that with extended abstinence, women recover gait and balance function to a level comparable with men.