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.     

Altered White Matter Integrity in Adolescent Binge Drinkers

Background:  White matter integrity has been found to be compromised in adult alcoholics, but it is unclear when in the course of alcohol exposure white matter abnormalities become apparent. This study assessed microstructural white matter integrity among adolescent binge drinkers with no history of an alcohol use disorder.
Methods:  We used diffusion tensor imaging to examine fractional anisotropy (FA), a measure of directional coherence of white matter tracts, among teens with ( n  =   14) and without ( n  =   14) histories of binge drinking but no history of alcohol use disorder, matched on age, gender, and education.
Results:  Binge drinkers had lower FA than controls in 18 white matter areas (clusters ≥27 contiguous voxels, each with p  < 0.01) throughout the brain, including the corpus callosum, superior longitudinal fasciculus, corona radiata, internal and external capsules, and commissural, limbic, brainstem, and cortical projection fibers, while exhibiting no areas of higher FA. Among binge drinkers, lower FA in 6 of these regions was linked to significantly greater lifetime hangover symptoms and/or higher estimated peak blood alcohol concentrations.
Conclusions:  Binge drinking adolescents demonstrated widespread reductions of FA in major white matter pathways. Although preliminary, these results could indicate that infrequent exposure to large doses of alcohol during youth may compromise white matter fiber coherence.     

Effects of family history of alcohol use disorders on spatial working memory BOLD response in adolescents

Background:  A positive family history (FH) of alcohol use disorders (AUD) has been linked to increased risk for the development of AUD, and neurocognitive factors have been postulated as important underlying mechanisms of familial alcoholism transmission.
Methods:  We used functional magnetic resonance imaging (fMRI) during a spatial working memory (SWM) and vigilance paradigm to investigate potential neurodevelopmental differences linked to familial density of AUD in 72 adolescents aged 12 to 14 years.
Results:  Youth with denser family histories of AUD showed less activation during a simple vigilance condition relative to SWM in cingulate and medial frontal gyri (β = 0.28, p  = 0.03), and a trend for more relative activity during rest (β = −0.25, p  = 0.07) in this cluster.
Conclusions:  Youth with greater familial densities of AUD may be less successful at modulating activity of the default network, potentially indicating a greater propensity for task-independent thought or reduced inhibition of task-irrelevant processing. Failure to moderate activation of the default network may have implications for cognitive efficiency and goal directed behavior in youth with dense FH. Further, aberrant activation in cingulate regions may be linked to genetic variation in GABA receptor units, suggesting a useful endophenotype for risk associated with alcohol dependence.     

Characterization of White Matter Microstructure in Fetal Alcohol Spectrum Disorders

Background:  Exposure to alcohol during gestation is associated with CNS alterations, cognitive deficits, and behavior problems. This study investigated microstructural aspects of putative white matter abnormalities following prenatal alcohol exposure.
Methods:  Diffusion tensor imaging was used to assess white matter microstructure in 27 youth (age range: 8 to 18 years) with ( n  = 15) and without ( n  = 12) histories of heavy prenatal alcohol exposure. Voxelwise analyses, corrected for multiple comparisons, compared fractional anisotropy (FA) and mean diffusivity (MD) between groups, throughout the cerebrum.
Results:  Prenatal alcohol exposure was associated with low FA in multiple cerebral areas, including the body of the corpus callosum and white matter innervating bilateral medial frontal and occipital lobes. Fewer between-group differences in MD were observed.
Conclusions:  These data provide an account of cerebral white matter microstructural integrity in fetal alcohol spectrum disorders and support extant literature showing that white matter is a target of alcohol teratogenesis. The white matter anomalies characterized in this study may relate to the neurobehavioral sequelae associated with gestational alcohol exposure, especially in areas of executive dysfunction and visual processing deficits.     

Parietal Gray Matter Volume Loss Is Related to Spatial Processing Deficits in Long-Term Abstinent Alcoholic Men

Background:  We previously demonstrated relatively intact cognitive function (with the exception of suggestive evidence for persistent deficits in spatial information processing) in middle-aged long-term abstinent alcoholics (LTAA, abstinent for 6 months or more) compared to age and gender comparable nonalcoholic controls (NAC) ( Fein et al., 2006 ).
Methods:  In the current study, we examine cortical gray matter volumes in the same samples to determine whether gray matter volumes in LTAA are consistent with the cognitive results – i.e., exhibiting gray matter volumes comparable to NAC in most brain regions, except for possible indications of persistent shrinkage in the parietal lobe subserving spatial information processing.
Results:  We found gray matter shrinkage in LTAA in the parietal lobe consistent with the spatial processing deficits in this same sample. More compelling, in LTAA, the magnitude of parietal gray matter shrinkage was negatively associated with spatial processing domain performance and positively associated with alcohol dose. Gray matter volume deficits were present in the occipital and other cortical tissue, but poorer visuospatial test performance correlated significantly with smaller volumes in the parietal cortex only.
Conclusions:  Taken together, the cognitive and structural imaging data provide compelling evidence that chronic alcohol abuse results in shrinkage of the parietal cortex with associated deficits in spatial information processing.     

Age-Related Gray Matter Shrinkage in a Treatment Naïve Actively Drinking Alcohol-Dependent Sample

Background:  We previously demonstrated, in a small sample, steeper age-related gray matter shrinkage in treatment naïve alcohol-dependent (TxN) men compared to nonalcoholic controls, but could not separate out the contributions of age and lifetime duration of alcohol use (which were highly correlated) to this effect. In the current study, we have quadrupled the sample size and expanded it to include both men and women to try to replicate and extend the previous findings and to separate the contributions of age and alcohol use to the phenomenon.
Methods:  In the current study, we examine cortical gray matter volumes in 18- to 50-year-old TxN ( n  = 84) versus age and gender comparable controls ( n  = 67). We used a new Region of Interest Analysis method which accounts for differences in sulcal and gyral enfolding between individuals ( Fein et al., 2009a ).
Results:  We found greater age-related gray matter shrinkage in TxN than in controls. Partial correlation analysis showed that the effect was a function of age and not lifetime alcohol burden.
Conclusions:  Implications of the findings are discussed in terms of their contribution toward our knowledge of differences between different subpopulations of alcoholics and in terms of their implications for the morbidity of alcohol dependence in an aging national population.     

Characterization of South African adolescents with alcohol use disorders but without psychiatric or polysubstance comorbidity

Background: Individuals who begin drinking during early adolescence and exhibit externalizing pathology and disinhibitory/dysregulatory tendencies are more vulnerable to developing alcohol use disorders (AUDs) in adulthood. Previous research has focused on in‐treatment populations with substantial comorbid psychopathology and polysubstance use. Here, we characterize a unique sample of treatment‐naïve adolescents without such comorbidity to help identify vulnerable youth who may benefit from early intervention. Methods: We compared externalizing propensity, disinhibitory characteristics, and school performance in adolescents with AUDs (but without comorbid psychopathology or other substance use; n = 70) to those of demographically matched controls (n = 70). Within the AUD group, we compared measures of substance use and the disinhibitory syndrome between boys and girls with differing severity of externalizing propensity. Results: Adolescents with AUDs demonstrated more externalizing propensity and disinhibitory personality traits (impulsivity, novelty seeking, and excitement seeking), poorer self‐monitoring and response inhibition, more bullying and sexual risk‐taking behavior, poorer first‐language performance, and greater use of alcohol, cannabis, and nicotine (p < 0.05). Within the AUD group, participants with higher externalizing propensity began drinking earlier, more frequently, and for a longer duration than those with lower externalizing symptoms (p < 0.05). Disinhibitory features (personality, cognition, and behavior) were, however, not stronger in those with higher externalizing propensity. Conclusions: We suggest that the constructs of externalizing propensity and disinhibitory syndrome are useful in characterizing treatment‐naïve adolescents with AUDs but without comorbid psychopathology or polysubstance use. These results support the importance of these constructs in understanding adolescent AUDs, even when the frank externalizing diagnoses of childhood (oppositional defiant disorder and conduct disorder) are excluded.     

Diffusion tensor measures of the corpus callosum in adolescents with adolescent onset alcohol use disorders

Background: In adults, myelination injury is associated with alcoholism. Maturation of the corpus callosum is prominent during adolescence. We hypothesized that subjects with adolescent‐onset alcohol use disorders (AUD; defined as Diagnostic and Statistical Manual of Mental Disorders‐IV alcohol dependence or abuse) would have myelination mircostructural differences compared to controls. Methods: Adolescent subjects (25 males, 7 females) with an AUD (16.9 ± 1.2 years), who were recruited from substance abuse treatment programs and had co‐morbid mental disorders, and 28 sociodemographically similar healthy controls (17 males, 11 females; 15.9 ± 1.1 years) underwent a 3.0 T MRI diffusion tensor imaging scan. Results: Measures of rostral body fractional anisotropy (FA) were higher in the AUD group than in the control group. Compared to controls, mean diffusivity (MD) was lower, while FA was higher, in the AUD group in the isthmus region. Anterior corpus callosum mircostructural development differed in adolescents with AUD, as age was positively (not negatively) associated with rostrum MD and age was negatively (not positively) associated with rostrum FA. There were sex by group interactions in that control females had higher posterior midbody FA when compared to female adolescents with AUD. Conclusions: Lower MD and higher FA values in the AUD group suggest pre‐morbid vulnerability for accelerated prefrontal and temporo‐parietal myelin maturation that may enhance the risk for adolescent AUD. Significant (and opposite to developmentally expected) correlations were seen between anterior corpus callosum MD and FA measures and age in the AUD group, suggesting neurotoxic effects of alcohol on adolescent corpus callosum microstructure. As seen in adults, female adolescents with AUD may be especially vulnerable to corpus callosum mircostructural injury. Further diffusion tensor imaging studies of corpus callosum maturation in children at familial risk for alcoholism, and in those with AUD, need to be done to elucidate these mechanisms.     

Initial Evidence of an Association Between OPRM1 and Adolescent Alcohol Misuse

Background:  Considerable research efforts have attempted to identify genes associated with alcoholism among adults, yet few studies have examined adolescents. Identifying genes associated with alcohol misuse in youth is important given that the relative contribution of genetic and environmental influences on alcoholism varies across development. The purpose of this study was to examine the association between a polymorphism of the μ-opioid receptor gene (OPRM1) and alcohol misuse in a sample of youth and to test whether heightened sensitivity to the reinforcing effects of alcohol mediated this relationship.
Methods:  Adolescents ( n  =   187; mean age = 15.4 years; 47.6% female) were genotyped for A118G (rs1799971), a single-nucleotide polymorphism (SNP) of the OPRM1 gene, and assessed for alcohol use disorder (AUD) diagnoses and other psychopathology. Alcohol misuse was also measured continuously to maximize detection of drinking problems in youth. Drinking motives were used to capture the extent to which youth consumed alcohol to enhance positive affect.
Results:  AUD groups differed significantly in terms of allelic distributions of the A118G SNP, such that 51.9% of youth with an AUD carried at least one copy of the G allele compared to 16.3% of non-AUD controls. Those who carried the G allele endorsed drinking to enhance positive affect more strongly than those who were homozygous for the A allele and drinking to enhance positive affect mediated the association between OPRM1 and alcohol-related problems.
Conclusions:  These data build on findings from adult studies and provide the first evidence that a polymorphism of the OPRM1 receptor gene is associated with the development of early-onset alcohol-related problems during adolescence, in part, by heightening sensitivity to the reinforcing effects of alcohol.     

Impulsivity, age of first alcohol use and substance use disorders among male adolescents: a population based case–control study

Aims   To evaluate the association between impulsivity, age of first alcohol consumption (AFD) and substance use disorders (SUD) in a non-clinical sample of adolescents.
Design and setting   Population-based case–control study of male adolescents between 15 and 20 years of age nested in a community survey in southern Brazil.
Participants   Cases were drug or alcohol abusers/dependents defined according to DSM-IV abuse/dependence criteria ( n  = 63). Individuals who had experienced alcohol use but where non-abusers served as controls ( n  = 355). Cases and controls completed a structured face-to-face interview.
Measurements   The Mini International Neuropsychiatric Interview (MINI) was completed during the original survey and used to identify cases and controls. Impulsivity was measured by means of the Barratt Impulsivity Scale (BIS 11). Self-reported AFD and socio-demographic data were collected and analyzed through logistic regression according to a hierarchical model.
Findings   Impulsivity and AFD were significantly associated with SUD. Both higher impulsivity [odds ratio (OR) 3.3, 95% confidence interval (CI) 1.4–7.8] and earlier AFD (OR 1.2, 95% CI 1.0–1.3) remained associated with SUD after model adjustments.
Conclusions   The findings from this population-based case–control study suggest that impulsivity and age of first alcoholic drink are associated strongly with alcohol and drug problems. Additionally, impulsivity seems to contribute to a premature exposure to alcohol by hastening the AFD. If the temporal effect of these associations is confirmed in longitudinal designs including broader population groups, our findings may contribute to the development of clinical and policy interventions aiming at reducing the incidence and morbidity associated with substance-related problems among adolescents.     

Extensive deep gray matter volume reductions in children and adolescents with fetal alcohol spectrum disorders

Background: The link between the numerous cognitive, motor, and behavioral difficulties of individuals with fetal alcohol spectrum disorders (FASD) and underlying specific structural brain injuries can be investigated using high‐resolution imaging. Differential sensitivity of the brain’s “relay” stations, namely the deep gray matter structures, may play a key factor given their multifaceted role in brain function. The purpose of our study was to analyze differences in deep gray matter volumes of children and adolescents with FASD relative to age/sex‐matched controls and to examine whether any volume differences were consistent across the age range of neurodevelopment. Methods: Children and adolescents (N = 28, 6 to 17 years) diagnosed with FASD and 56 age‐ and sex‐matched healthy controls (i.e., 2 matched controls per FASD subject) underwent 3‐dimensional T1‐weighted MRI scans that were used for the automated volume measurement (FreeSurfer) of the intracranial space, total white matter, cortical gray matter, and 6 deep gray matter structures, namely the hippocampus, amygdala, thalamus, caudate, putamen, and globus pallidus, with left and right measured separately. Volumes were compared between FASD and controls, as well as changes with age. Results: Significant reductions of volume in FASD were observed for the intracranial vault (7.6%), total white matter (8.6%), total cortical gray matter (7.8%), and total deep gray matter (13.1%). All 6 deep gray matter structures showed significant volume reductions bilaterally with the caudate (approximately 16%) and globus pallidus (approximately 18%) being most affected. The hippocampus, thalamus, and globus pallidus showed reductions in all 3 age subgroups (6 to 9, 10 to 13, and 14 to 17 years) but the caudate and putamen had smaller volumes for FASD only within the 2 youngest subgroups; the amygdala was only smaller for FASD in the 2 oldest subgroups. Conclusions: Significant, but variable, volume reductions throughout the deep gray matter are observed over a wide age range of 6 to 17 years in FASD.     

Hope,coping skills,and the prefrontal cortex in alcohol use disorder recovery

Background: Alcohol use disorders adversely affect individual and societal health. These disorders are a chronic brain disease, and protective factors against relapse should be studied. Prefrontal cortex (PFC) dysfunction is evident in alcohol use disorders, and research that explores recovery of the PFC in alcohol use disorders is needed, specifically in regard to how psychological and behavioral factors can augment medicalized treatments and protect against relapse. For example, hope or a belief that recovery is possible is an important cognitive construct—thought to precede behavioral action—that has been associated with relapse. Objectives: In this study, associations between healthy coping skills and hope (psychological/behavioral factors) and PFC regional activation in response to alcohol cue exposure were examined. It was also examined whether such associations were unique to alcohol cues. Methods: Forty-two participants, 32 males and nine females in recovery from an alcohol use disorder (AUD), were administered a subjective hope and coping in recovery measure. They also viewed alcohol, positive, negative, and neutral cues during functional near-infrared spectroscopy (fNIR) PFC assessment. Results: Levels of healthy coping skills positively correlated with activation in the right dorsomedial prefrontal cortex (DMPFC) in response to alcohol cues. This finding was unique to alcohol cues. Conclusion: The association between coping skills and activation of the right DMPFC in response to alcohol cues may reflect greater action restraint and top-down PFC control processing that may protect against relapse.     

Decision making in alcohol dependence: insensitivity to future consequences and comorbid disinhibitory psychopathology

Background:  Alcohol dependence (AD) is often comorbid with other disinhibitory disorders that are characterized by poor decision making and evidenced by disadvantageous strategies on laboratory tasks such as the Iowa Gambling Task (IGT). In this study, a variant of the IGT is used to examine specific mechanisms that may account for poor decision making on the task in AD both with and without comorbid psychopathology.
Methods:  The community sample ( n  = 428) included 134 young adult subjects with AD and a history of childhood conduct disorder (CCD), 129 with AD and no history of CCD, 60 with a history of CCD and no AD, and 105 controls. Lifetime histories of other disinhibitory problems (adult antisocial behavior, marijuana, and other drugs) and major depression also were assessed. A modified version of the IGT was used to estimate (i) insensitivity to future consequences (IFC), and (ii) preference for large versus small immediate reward decks (PLvS).
Results:  Both AD and CCD were associated with greater IFC but not greater PLvS. Structural equation models (SEMs) indicated that IFC was associated with higher scores on a latent dimensional "disinhibitory disorders" factor representing the covariance among all lifetime measures of disinhibitory psychopathology, but was not directly related to any one disinhibitory disorder. SEMs also suggested that adult antisocial behavior was uniquely associated with a greater PLvS.
Conclusions:  Disadvantageous decision making on the IGT in those with AD and related disinhibitory disorders may reflect an IFC that is common to the covariance among these disorders but not unique to any one disorder.     

Frontal white matter and cingulum diffusion tensor imaging deficits in alcoholism

Background:  Alcoholism-related deficits in cognition and emotion point toward frontal and limbic dysfunction, particularly in the right hemisphere. Prefrontal and anterior cingulate cortices are involved in cognitive and emotional functions and play critical roles in the oversight of the limbic reward system. In the present study, we examined the integrity of white matter tracts that are critical to frontal and limbic connectivity.
Methods:  Diffusion tensor magnetic resonance imaging (DT-MRI) was used to assess functional anisotropy (FA), a measure of white matter integrity, in 15 abstinent long-term chronic alcoholic and 15 demographically equivalent control men. Voxel-based and region-based analyses of group FA differences were applied to these scans.
Results:  Alcoholic subjects had diminished frontal lobe FA in the right superior longitudinal fascicles II and III, orbitofrontal cortex white matter, and cingulum bundle, but not in corresponding left hemisphere regions. These right frontal and cingulum white matter regional FA measures provided 97% correct group discrimination. Working Memory scores positively correlated with superior longitudinal fascicle III FA measures in control subjects only.
Conclusions:  The findings demonstrate white matter microstructure deficits in abstinent alcoholic men in several right hemisphere tracts connecting prefrontal and limbic systems. These white matter deficits may contribute to underlying dysfunction in memory, emotion, and reward response in alcoholism.     

Relationship between Alcohol Withdrawal Seizures and Temporal Lobe White Matter Volume Deficits

A previous magnetic resonance imaging study from our laboratory reported significant temporal lobe volume deficits in cortical gray matter, white matter, and anterior hippocampus in chronic alcoholic men relative to controls. In the present study, we reexamined these data and asked whether withdrawal seizure history was predictive of either the hippocampal or the extrahippocampal volume deficits. A review of the medical charts indicated that 11 alcoholics had experienced one or more alcohol-related seizures and 35 were seizure-free; no patient had a seizure disorder unrelated to alcohol. The two alcoholic groups did not differ significantly in age, education, alcohol consumption variables, premorbid intelligence, Memory Quotient, Trail Making, or detection of hidden figures. Although each alcoholic group showed significant bilateral volume deficits of the anterior hippocampus and frontal-parietal and temporal gray matter, relative to controls, the seizure group had significantly smaller temporal lobe white matter volumes than either the control or the seizure-free groups; the latter two groups did not differ from each other. Both alcoholic groups, however, had white matter volume deficits in the frontal-parietal region. Thus, the seizure group accounted for the white matter volume deficits in the temporal lobe previously reported in the full sample of alcoholics. It seems, then, that reduced white matter volume in the temporal lobes may be either a risk factor for or sequela of alcohol withdrawal seizures.     

Genetic and non-genetic influences on the development of co-occurring alcohol problem use and internalizing symptomatology in adolescence: a review

Aims   Alcohol problem use during adolescence has been linked to a variety of adverse consequences, including cigarette and illicit drug use, delinquency, adverse effects on pubertal brain development and increased risk of morbidity and mortality. In addition, heavy alcohol-drinking adolescents are at increased risk of comorbid psychopathology, including internalizing symptomatology (especially depression and anxiety). A range of genetic and non-genetic factors have been implicated in both alcohol problem use as well as internalizing symptomatology. However, to what extent shared risk factors contribute to their comorbidity in adolescence is poorly understood.
Design   We conducted a systematic review on Medline, PsycINFO, Embase and Web of Science to identify epidemiological and molecular genetic studies published between November 1997 and November 2007 that examined risk factors that may be shared in common between alcohol problem use and internalizing symptomatology in adolescence.
Findings   Externalizing disorders, family alcohol problems and stress, as well as the serotonin transporter ( 5-HTT ) S-allele, the monoamine oxidase A ( MAOA ) low-activity alleles and the dopamine D2 receptor ( DDR2 ) Taq A1 allele have been associated most frequently with both traits. An increasing number of papers are focusing upon the role of gene–gene (epistasis) and gene–environment interactions in the development of comorbid alcohol problem use and internalizing symptomatology.
Conclusions   Further research in adolescents is warranted; the increasing availability of large longitudinal genetically informative studies will provide the evidence base from which effective prevention and intervention strategies for comorbid alcohol problems and internalizing symptomatology can be developed.     

Posttraumatic Stress Disorder and Alcohol Use Disorder: A Critical Review of Pharmacologic Treatments

Treatment of alcohol use disorder (AUD) is complicated by the presence of psychiatric comorbidity including posttraumatic stress disorder (PTSD). This is a critical review of the literature to date on pharmacotherapy treatments of AUD and PTSD. A systematic literature search using PubMed MESH terms for alcohol and substance use disorders, PTSD, and treatment was undertaken to identify relevant randomized controlled trials (RCTs). The studies were independently evaluated (ILP and TLS) and those that evaluated the efficacy of a pharmacotherapy for individuals diagnosed with AUD and PTSD and were RCTs were selected. Studies were grouped in 3 categories: (i) those that evaluated first‐line treatments for PTSD, (ii) those that evaluated medications to target AUD, and (iii) those that evaluated medications hypothesized to be effective in targeting alcohol consumption as well as PTSD symptoms. Nine RCTs were identified; 3 focused on medications to treat PTSD, 4 focused on AUD, and 3 to target both. One study included both a medication to treat PTSD and 1 to treat AUD so was discussed twice. All but 1 of the studies found that PTSD symptoms and drinking outcomes improved significantly over time. There is not 1 agent with clear evidence of efficacy in this comorbid group. The results for medications to treat PTSD are inconclusive because of contradictory results. There was weak evidence to support the use of medications to treat AUD among those with comorbidity with PTSD. Findings for medications that were hypothesized to treat both disorders were also contradictory. Most studies provided a combination of interventions to treat both disorders. Despite the contradictory results, this review suggests that individuals with AUD and comorbid PTSD can safely be prescribed medications used in noncomorbid populations and patients improve with treatment.     

Alcohol and Colorectal Cancer: The Role of Alcohol Dehydrogenase 1C Polymorphism

Background:  Chronic alcohol consumption is a risk factor for colorectal cancer. Animal experiments as well as genetic linkage studies in Japanese individuals with inactive acetaldehyde dehydrogenase leading to elevated acetaldehyde concentrations following ethanol ingestion support the hypothesis that acetaldehyde may be responsible for this carcinogenic effect of alcohol. In Caucasians, a polymorphism of alcohol dehydrogenase 1C ( ADH1C ) exists resulting in different acetaldehyde concentrations following ethanol oxidation.
Methods:  To evaluate whether the association between alcohol consumption and colorectal tumor development is modified by ADH1C polymorphism, we recruited 173 individuals with colorectal tumors diagnosed by colonoscopy and 788 control individuals without colorectal tumors. Genotyping was performed using genomic DNA extracted from whole blood followed by polymerase chain reaction.
Results:  Genotype ADH1C*1/1 was more frequent in patients with alcohol-associated colorectal neoplasia compared to patients without cancers in the multivariate model controlling for age, gender, and alcohol intake (odds ratio = 1.674, 95% confidence interval = 1.110–2.524, 2-sided p from Wald test = 0.0139). In addition, the joint test of the genetic effect and interaction between ADH1C genotype and alcohol intake (2-sided p  = 0.0007) indicated that the difference in ADH1C*1 polymorphisms between controls and colorectal neoplasia is strongly influenced by the alcohol consumption and that only individuals drinking more than 30 g ethanol per day with the genotype ADH1C*1/1 had an increased risk for colorectal tumors.
Conclusions:  These data identify ADH1C homozygosity as a genetic risk marker for colorectal tumors in individuals consuming more than 30 g alcohol per day and emphasize the role of acetaldehyde as a carcinogenic agent in alcohol-related colorectal carcinogenesis.     

A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Naltrexone in Outpatients With Bipolar Disorder and Alcohol Dependence

Background:  Alcohol dependence is extremely common in patients with bipolar disorder and is associated with unfavorable outcomes including treatment nonadherence, violence, increased hospitalization, and decreased quality of life. While naltrexone is a standard treatment for alcohol dependence, no controlled trials have examined its use in patients with co-morbid bipolar disorder and alcohol dependence. In this pilot study, the efficacy of naltrexone in reducing alcohol use and on mood symptoms was assessed in bipolar disorder and alcohol dependence.
Methods:  Fifty adult outpatients with bipolar I or II disorders and current alcohol dependence with active alcohol use were randomized to 12 weeks of naltrexone (50 mg/d) add-on therapy or placebo. Both groups received manual-driven cognitive behavioral therapy designed for patients with bipolar disorder and substance-use disorders. Drinking days and heavy drinking days, alcohol craving, liver enzymes, and manic and depressed mood symptoms were assessed.
Results:  The 2 groups were similar in baseline and demographic characteristics. Naltrexone showed trends ( p  < 0.10) toward a greater decrease in drinking days (binary outcome), alcohol craving, and some liver enzyme levels than placebo. Side effects were similar in the 2 groups. Response to naltrexone was significantly related to medication adherence.
Conclusions:  Results suggest the potential value and acceptable tolerability of naltrexone for alcohol dependence in bipolar disorder patients. A larger trial is needed to establish efficacy.     

The Effect of Past Abuse on PFC Recovery from an Alcohol Use Disorder

ABSTRACT

The purpose of this study was to examine the impact of trauma on Alcohol Use Disorders (AUD) and recovery, specifically through examining associations between past trauma and prefrontal cortex activation in response to alcohol cues. This study utilized functional near-infrared spectroscopy (fNIR) to evaluate activation of the PFC in individuals in recovery for an AUD when presented with positive, negative, neutral, and alcohol related images. Results showed that a history of trauma and length of recovery are associated with PFC responses to affective images for individuals in recovery. These findings suggest that the PFC of individuals in recovery from AUD who have been physically abused exhibit a more hyperactive response to surroundings, but this hyperactivity may decrease over time as recovery length increases. Those in recovery from AUD who do not report a history of physical abuse demonstrate reduced PFC activation in response to affective images, however, this activity increases as recovery progresses. Additionally, the results showed a significant but opposite pattern with respect to reporting a history of emotional abuse. Authors recommend that clinicians working with those seeking recovery from AUD provide psychotherapy that addresses the complex relationship between PFC functioning, trauma, and AUD and provides an individualized recovery process.