Microstructural Corpus Callosum Anomalies in Children With Prenatal Alcohol Exposure: An Extension of Previous Diffusion Tensor Imaging Findings

Background: Several studies have now shown corpus callosum abnormalities using diffusion tensor imaging (DTI) in children with fetal alcohol spectrum disorders (FASD) in comparison with nonexposed controls. The data suggest that posterior regions of the callosum may be disproportionately affected. The current study builds on previous efforts, including our own work, and moves beyond midline corpus callosum to probe major inter‐hemispheric white matter pathways with an improved DTI tractographic method. This study also expands on our prior work by evaluating a larger sample and by incorporating children with a broader range of clinical effects including full‐criteria fetal alcohol syndrome (FAS). Methods: Participants included 33 children with FASD (8 FAS, 23 partial FAS, 2 static encephalopathy) and 19 nonexposed controls between the ages of 10 and 17 years. Participants underwent DTI scans and intelligence testing. Groups (FASD vs. controls) were compared on fractional anisotropy (FA) and mean diffusivity (MD) in 6 white matter tracts projected through the corpus callosum. Exploratory analyses were also conducted examining the relationships between DTI measures in the corpus callosum and measures of intellectual functioning and facial dysmorphology. Results: In comparison with the control group, the FASD group had significantly lower FA in 3 posterior tracts of the corpus callosum: the posterior mid‐body, the isthmus, and the splenium. A trend‐level finding also suggested lower FA in the genu. Measures of white matter integrity and cognition were correlated and suggest some regional specificity, in that only posterior regions of the corpus callosum were associated with visual‐perceptual skills. Correlations between measures of facial dysmorphology and posterior regions of the corpus callosum were nonsignificant. Conclusions: Consistent with previous DTI studies, these results suggest that microstructural posterior corpus callosum abnormalities are present in children with prenatal alcohol exposure and cognitive impairment. These abnormalities are clinically relevant because they are associated with cognitive deficits and appear to provide evidence of abnormalities associated with prenatal alcohol exposure independent of dysmorphic features. As such, they may yield important diagnostic and prognostic information not provided by the traditional facial characteristics.     

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.     

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.     

Diffusion tensor imaging in children with fetal alcohol spectrum disorders

BACKGROUND: Prenatal alcohol exposure, which is associated with macrostructural brain abnormalities, neurocognitive deficits, and behavioral disturbances, is characterized as fetal alcohol syndrome (FAS) in severe cases. The only published study thus far using diffusion tensor imaging (DTI) showed microstructural abnormalities in patients with FAS. The current study investigated whether similar abnormalities are present in less severely affected, prenatally exposed patients who did not display all of the typical FAS physical stigmata. METHODS: Subjects included 14 children, ages 10 to 13, with fetal alcohol spectrum disorders (FASD) and 13 matched controls. Cases with full-criteria FAS, mental retardation, or microcephaly were excluded. Subjects underwent MRI scans including DTI. RESULTS: Although cases with microcephaly were excluded, there was a trend toward smaller total cerebral volume in the FASD group (p=0.057, Cohen's d effect size =0.73). Subjects with FASD had greater mean diffusivity (MD) in the isthmus of the corpus callosum than controls (p=0.013, effect size =1.05), suggesting microstructural abnormalities in this region. There were no group differences in 5 other regions of the corpus callosum. Correlations between MD in the isthmus and facial dysmorphology were nonsignificant. CONCLUSIONS: These results suggest that even relatively mild forms of fetal alcohol exposure may be associated with microstructural abnormalities in the posterior corpus callosum that are detectable with DTI.     

In vivo detection and functional correlates of white matter microstructural disruption in chronic alcoholism

BACKGROUND: Postmortem studies report degradation of brain white matter microstructure in chronic alcoholism, but until recently, in vivo neuroimaging could provide measurement only at a macrostructural level. The development of magnetic resonance diffusion tensor imaging (DTI) for clinical use offers a method for depicting and quantifying the diffusion properties of white matter expressed as intravoxel and intervoxel coherence of tracts and fibers. METHODS: This study used DTI to examine the intravoxel coherence measured as fractional anisotropy (FA) and intervoxel coherence (C) of white matter tracts of the genu and splenium of the corpus callosum and of the centrum semiovale in 15 detoxified alcoholic men and 31 nonalcoholic control subjects. Exploratory correlational analyses examined the relationships between regional DTI measures and tests of attention and working memory in the alcoholic patients. RESULTS: The alcoholic group had lower regional FA than the control group. C was lower in the alcoholics than controls in the splenium only. Working memory correlated positively with splenium FA, whereas attention correlated positively with genu C. CONCLUSIONS: These results provide in vivo evidence for disruption of white matter microstructure in alcoholism and suggest that interruption of white matter fiber coherence contributes to disturbance in attention and working memory in chronic alcoholism.     

Prefrontal cortex volumes in adolescents with alcohol use disorders: unique gender effects

Background:  Adolescents with alcohol use disorders (AUD) have shown smaller prefrontal cortex (PFC) volumes compared with healthy controls; however, differences may have been due to comorbid disorders. This study examined PFC volumes in male and female adolescents with AUD who did not meet criteria for comorbid mood or attention disorders.
Methods:  Participants were adolescents aged 15 to 17 who met criteria for AUD ( n  = 14), and demographically similar healthy controls ( n  = 17). Exclusions included any history of a psychiatric or neurologic disorder other than AUD or conduct disorder. Magnetic resonance imaging scans occurred after at least 5 days of abstinence from alcohol or drugs. Overall PFC volumes and white matter PFC volumes were compared between groups.
Results:  After controlling for conduct disorder, gender, and intracranial volume, AUD teens demonstrated marginally smaller anterior ventral PFC volumes ( p  = 0.09) than controls, and significant interactions between group and gender were observed ( p  < 0.001 to p  < 0.03). Compared with same-gender controls, females with AUD demonstrated smaller PFC volumes, while males with AUD had larger PFC volumes. The same pattern was observed for PFC white matter volumes.
Conclusions:  Consistent with adult literature, alcohol use during adolescence is associated with prefrontal volume abnormalities, including white matter differences. However, adolescents with AUD demonstrated gender-specific morphometric patterns. Thus, it is possible that gender may moderate the impact of adolescent alcohol use on prefrontal neurodevelopment, and the neurodevelopmental trajectories of heavy drinking boys and girls should be evaluated separately in longitudinal studies.     

Ventricular expansion in wild-type Wistar rats after alcohol exposure by vapor chamber

Background: Structural magnetic resonance imaging (MRI) reveals widespread brain damage manifest as tissue shrinkage and complementary ventriculomegaly in human alcoholism. For an animal model to parallel the human condition, high alcohol exposure should produce similar radiologically detectable neuropathology. Our previous structural MRI study demonstrated only modest brain dysmorphology of the alcohol‐preferring (P) rat with average blood alcohol levels (BALs) of 125 mg/dl achieved with voluntary consumption. Here, we tested the hypothesis that wild‐type Wistar rats, exposed to vaporized alcohol ensuring higher BALs than typically achieved with voluntary consumption in rodents, would model MRI findings in the brains of humans with chronic alcoholism. Methods: The longitudinal effects of vaporized alcohol exposure on the brains of 10 wild‐type Wistar rats compared with 10 sibling controls were investigated with structural MRI, conducted before (MRI 1) and after (MRI 2) 16 of alcohol exposure and after an additional 8 weeks at a higher concentration of alcohol (MRI 3). Results: Two rats in the alcohol group died prior to MRI 2. The remaining vapor‐exposed rats (n = 8) achieved BALs of 293 mg/dl by MRI 2 and 445 mg/dl by MRI 3. Whereas the controls gained 17% of their body weight from MRI 1 to MRI 3, the alcohol‐exposed group lost 6%. MRI, quantified with atlas‐based parcellation, revealed a profile of significant ventricular expansion, after alcohol vapor exposure, in 9 contiguous slices, extending from the dorsolateral to ventrolateral ventricles. In particular, from MRI 1 to MRI 2, this ventricular volume expanded by an average of 6.5% in the controls and by 27.1% in the alcohol‐exposed rats but only an additional 1.5% in controls and 2.4% in alcohol‐exposed rats from MRI 2 to MRI 3. The midsagittal volume of the full anterior‐to‐posterior extent of the corpus callosum grew between the first 2 MRIs in both groups followed by regression in the alcohol group by MRI 3. Although group differences were statistically significant, among animals there was substantial variability of the effects of alcohol exposure on brain morphology; some animals showed profound effects, whereas others were essentially unaffected. Conclusions: The ventricular dilatation and callosal shrinkage produced in wild‐type rats following involuntary alcohol exposure yielded a modestly successful model of neurodysmorphology phenotypes of human alcoholism. As is the case for the human condition, however, in which some individuals express greater alcoholism‐related neuropathology than others, some rats may be more susceptible than others to extreme alcohol exposure.     

Delay Discounting Behavior and White Matter Microstructure Abnormalities in Youth With a Family History of Alcoholism

Background: Youth with family history of alcohol abuse have a greater risk of developing an alcohol use disorder (AUD). Brain and behavior differences may underlie this increased vulnerability. The current study examined delay discounting behavior and white matter microstructure in youth at high risk for alcohol abuse, as determined by a family history of alcoholism (FH+), and youth without such family history (FH?). Methods: Thirty‐three healthy youth (FH+ = 15, FH? = 18), ages 11 to 15 years, completed a delay discounting task and underwent diffusion tensor imaging. Tract‐based spatial statistics ( Smith et al., 2006 ), as well as follow‐up region‐of‐interest analyses, were performed to compare fractional anisotropy (FA) between FH+ and FH? youth. Results: FH+ youth showed a trend toward increased discounting behavior and had significantly slower reaction times (RTs) on the delay discounting paradigm compared to FH? youth. Group differences in FA were seen in several white matter tracts. Furthermore, lower FA in the left inferior longitudinal fasciculus and the right optic radiation statistically mediated the relationship between FH status and slower RTs on the delay discounting task. Conclusions: Youth with a family history of substance abuse have disrupted white matter microstructure, which likely contributes to less efficient cortical processing and may act as an intrinsic risk factor contributing to an increased susceptibility of developing AUD. In addition, FHP youth showed a trend toward greater impulsive decision making, possibly representing an inherent personal characteristic that may facilitate substance use onset and abuse in high‐risk youth.     

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.     

Demonstration of interstitial cerebral edema with diffusion tensor MR imaging in type C hepatic encephalopathy

Brain water may increase in hepatic encephalopathy (HE). Diffusion tensor imaging was performed in patients with cirrhosis with or without HE to quantify the changes in brain water diffusivity and to correlate it with neuropsychological (NP) tests. Thirty-nine patients with cirrhosis, with minimal (MHE) or overt HE, were studied and compared to 18 controls. Mean diffusivity (MD) and fractional anisotropy (FA) were calculated in corpus callosum, internal capsule, deep gray matter nuclei, periventricular frontal, and occipital white matter regions in both cerebral hemispheres. The MD and FA values from different regions in different groups were compared using analysis of variance and Spearman's rank correlation test. In 10 patients with MHE, repeat studies were performed after 3 weeks of lactulose therapy to look for any change in MD, FA, and NP scores. Significantly increased MD was found with insignificant changes in FA in various regions of brain in patients with MHE or HE compared with controls, indicating an increase in interstitial water in the brain parenchyma without any microstructural changes. A significant correlation was found between MD values from corpus callosum, internal capsule, and NP test scores. After therapy, MD values decreased significantly and there was a corresponding improvement in NP test scores. Further analysis showed that MD values were different for different grades of minimal or overt HE. In conclusion, the increase in MD with no concomitant changes in FA in cirrhosis with minimal or early HE indicates the presence of reversible interstitial brain edema.     

Interhemispheric transfer in children with heavy prenatal alcohol exposure

BACKGROUND: Prenatal alcohol exposure has long been associated with alterations in brain structure and behavioral changes. The corpus callosum can be affected by heavy prenatal alcohol exposure, and agenesis (absence) of this structure occurs more often in children with fetal alcohol syndrome than in the general population or in other developmentally delayed populations. Although the majority of children with fetal alcohol syndrome do not have agenesis of the corpus callosum, callosal area is reduced in this population, particularly in the anterior and posterior regions. However, the functional implication of these size reductions has not been examined. METHODS: The current study used a finger localization task to measure the transfer of information across the corpus callosum in children and adolescents with histories of heavy prenatal alcohol exposure and age- and sex-matched controls. In a subset of children, correlational analysis was also conducted between behavioral data and cross-sectional area of the corpus callosum. RESULTS: When compared with nonexposed controls, alcohol-exposed children made more errors on trials for which information had to cross the corpus callosum ("crossed" trials) than on trials for which it did not ("uncrossed" trials), and they also made more errors as the task increased in complexity. Additionally, correlations with magnetic resonance imaging data in a subset of children revealed that impairment in interhemispheric transfer was related to reductions in the size of the corpus callosum. These correlations were independent of effects expected from the relationship between corpus callosum size and general intellectual functioning alone. CONCLUSIONS: These findings suggest that children with heavy prenatal alcohol exposure display subtle deficits in the interhemispheric transfer of information in the somatosensory domain. Such deficits in interhemispheric transfer are likely to be related to the myriad of other behavioral and cognitive impairments observed in these children.     

The Dimensionality of DSM-IV Alcohol Use Disorders Among Adolescent and Adult Drinkers and Symptom Patterns by Age, Gender, and Race/Ethnicity

Background: There is limited information on the validity of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM‐IV) alcohol use disorders (AUD) symptom criteria among adolescents in the general population. The purpose of this study is to assess the DSM‐IV AUD symptom criteria as reported by adolescent and adult drinkers in a single representative sample of the U.S. population aged 12 years and older. This design avoids potential confounding due to differences in survey methodology when comparing adolescents and adults from different surveys. Methods: A total of 133,231 current drinkers (had at least 1 drink in the past year) aged 12 years and older were drawn from respondents to the 2002 to 2005 National Surveys on Drug Use and Health. DSM‐IV AUD criteria were assessed by questions related to specific symptoms occurring during the past 12 months. Factor analytic and item response theory models were applied to the 11 AUD symptom criteria to assess the probabilities of symptom item endorsements across different values of the underlying trait. Results: A 1‐factor model provided an adequate and parsimonious interpretation for the 11 AUD criteria for the total sample and for each of the gender–age groups. The MIMIC model exhibited significant indication for item bias among some criteria by gender, age, and race/ethnicity. Symptom criteria for “tolerance,”“time spent,” and “hazardous use” had lower item thresholds (i.e., lower severity) and low item discrimination, and they were well separated from the other symptoms, especially in the 2 younger age groups (12 to 17 and 18 to 25). “Larger amounts,”“cut down,”“withdrawal,” and “legal problems” had higher item thresholds but generally lower item discrimination, and they tend to exhibit greater dispersion at higher AUD severity, particularly in the youngest age group (12 to 17). Conclusions: Findings from the present study do not provide support for the 2 separate DSM‐IV diagnoses of alcohol abuse and dependence among either adolescents or adults. Variations in criteria severity for both abuse and dependence offer support for a dimensional approach to diagnosis which should be considered in the ongoing development of DSM‐V.     

Associations between fractional anisotropy and problematic alcohol use in juvenile justice-involved adolescents

Abstract

Background: Studies have shown associations between heavy alcohol use and white matter alterations in adolescence. Youth involved with the juvenile justice system engage in high levels of risk behavior generally and alcohol use in particular as compared to their non-justice-involved peers. Objectives: This study explored white matter integrity among justice-involved adolescents. Analyses examined fractional anisotropy (FA) and mean diffusivity (MD) between adolescents with low and high levels of problematic alcohol use as assessed by the Alcohol Use Disorders Identification Test (AUDIT). Methods: Participants (N?=?125; 80% male; 14–18 years) completed measures assessing psychological status and substance use followed by diffusion tensor imaging (DTI). DTI data for low (n?=?51) and high AUDIT (n?=?74) adolescents were subjected to cluster-based group comparisons on skeletonized FA and MD data. Results: Whole-brain analyses revealed significantly lower FA in clusters in the right and left posterior corona radiata (PCR) and right superior longitudinal fasciculus (SLF) in the high AUDIT group, as well as one cluster in the right anterior corona radiata that showed higher FA in the high AUDIT group. No differences in MD were identified. Exploratory analyses correlated cluster FA with measures of additional risk factors. FA in the right SLF and left PCR was negatively associated with impulsivity. Conclusion: Justice-involved adolescents with alcohol use problems generally showed poorer FA than their low problematic alcohol use peers. Future research should aim to better understand the nature of the relationship between white matter development and alcohol use specifically as well as risk behavior more generally.     

The contribution of parental alcohol use disorders and other psychiatric illness to the risk of alcohol use disorders in the offspring

Background: Few population‐based studies have investigated associations between parental history of alcoholism and the risk of alcoholism in offspring. The aim was to investigate in a large cohort the risk of alcohol use disorders (AUD) in the offspring of parents with or without AUD and with or without hospitalization for other psychiatric disorder (OPD). Methods: Longitudinal birth cohort study included 7,177 men and women born in Copenhagen between October 1959 and December 1961. Cases of AUD were identified in 3 Danish health registers and cases of OPD in the Danish Psychiatric Central Register. Offspring registration with AUD was analyzed in relation to parental registration with AUD and OPD. Covariates were offspring gender and parental social status. Results: Both maternal and paternal registration with AUD significantly predicted offspring risk of AUD (odds ratios 1.96; 95% CI 1.42 to 2.71 and 1.99; 95% CI 1.54 to 2.68, respectively). The association between maternal, but not paternal, OPD and offspring AUD was also significant (odds ratios 1.46; 95% CI 1.15 to 1.86 and 1.26; 95% CI 0.95 to 1.66, respectively). Other predictors were male gender and parental social status. A significant interaction was observed between paternal AUD and offspring gender on offspring AUD, and stratified analyses showed particularly strong associations of both paternal and maternal AUD with offspring AUD in female cohort members. Conclusions: Parental AUD was associated with an increased risk of offspring AUD independent of other significant predictors, such as gender, parental social status, and parental psychiatric hospitalization with other diagnoses. Furthermore, this association appeared to be stronger among female than male offspring. The results suggest that inherited factors related to alcoholism are at least as important in determining the risk of alcoholism among daughters as among sons.     

Global–Local Interference is Related to Callosal Compromise in Alcoholism: A Behavior-DTI Association Study

Background: Visuospatial ability is a multifactorial process commonly impaired in chronic alcoholism. Identification of which features of visuospatial processing are affected and which are spared in alcoholism, however, has not been clearly determined. We used a global–local paradigm to assess component processes of visuospatial ability and MR diffusion tensor imaging (DTI) to examine whether alcoholism‐related microstructural degradation of the corpus callosum contributes to disruption of selective lateralized visuospatial and attention processes. Methods: A hierarchical letter paradigm was devised, where large global letters were composed of small local letters. The task required identification of target letters among distractors presented at global, local, both, or neither level. Attention was either selectively directed to global or local levels or divided between levels. Participants were 18 detoxified chronic alcoholics and 22 age‐matched healthy controls. DTI provided quantitative assessment of the integrity of corpus callosal white matter microstructure. Results: Alcoholics generally had longer reaction times than controls but obtained similar accuracy scores. Both groups processed local targets faster than global targets and showed interference from targets at the unattended level. Alcoholics exhibited moderate compromise in selectively attending to the global level when the global stimuli were composed of local targets. Such local interference was less with longer abstinence. Callosal microstructural integrity compromise predicted degree of interference from stimulus incongruency in the alcoholic group. This relationship was not observed for lateral or third ventricular volumes, which are measures of nonspecific cortical volume deficits. Conclusion: Global–local feature perception was generally spared in abstinent chronic alcoholics, but impairments were observed when directing attention to global features and when global and local information interfered at stimulus or response levels. Furthermore, the interference‐callosal integrity relationship in alcoholics indicates that compromised visuospatial functions include those requiring bilateral integration of information.     

Alcohol and depression

Aims To examine the literature on the associations between alcohol use disorders (AUD) and major depression (MD), and to evaluate the evidence for the existence of a causal relationship between the disorders. Methods PsycInfo; PubMed; Embase; Scopus; ISI Web of Science database searches for studies pertaining to AUD and MD from the 1980 to the present. Random‐effects models were used to derive estimates of the pooled adjusted odds ratios (AOR) for the links between AUD and MD among studies reporting an AOR. Results The analysis revealed that the presence of either disorder doubled the risks of the second disorder, with pooled AORs ranging from 2.00 to 2.09. Epidemiological data suggest that the linkages between the disorders cannot be accounted for fully by common factors that influence both AUD and MD, and that the disorders appear to be linked in a causal manner. Further evidence suggests that the most plausible causal association between AUD and MD is one in which AUD increases the risk of MD, rather than vice versa. Potential mechanisms underlying these causal linkages include neurophysiological and metabolic changes resulting from exposure to alcohol. The need for further research examining mechanisms of linkage, gender differences in associations between AUD and MD and classification issues was identified. Conclusions The current state of the literature suggests a causal linkage between alcohol use disorders and major depression, such that increasing involvement with alcohol increases risk of depression. Further research is needed in order to clarify the nature of this causal link, in order to develop effective intervention and treatment approaches.     

Adolescent substance abuse: the effects of alcohol and marijuana on neuropsychological performance

Background: Adolescence is a period in which cognition and brain undergo dramatic parallel development. Whereas chronic use of alcohol and marijuana is known to cause cognitive impairments in adults, far less is known about the effect of these substances of abuse on adolescent cognition, including possible interactions with developmental processes. Methods: Neuropsychological performance, alcohol use, and marijuana use were assessed in 48 adolescents (ages 12 to 18), recruited in 3 groups: a healthy control group (HC, n = 15), a group diagnosed with substance abuse or dependence (SUD, n = 19), and a group with a family history positive for alcohol use disorder (AUD) but no personal substance use disorder (FHP, n = 14). Age, drinks per drinking day (DPDD), percentage days drinking, and percentage days using marijuana were considered as covariates in a MANCOVA in which 6 neuropsychological composites (Verbal Reasoning, Visuospatial Ability, Executive Function, Memory, Attention, and Processing Speed) served as dependent variables. Results: More DPDD predicted poorer performance on Attention and Executive Function composites, and more frequent use of marijuana was associated with poorer Memory performance. In separate analyses, adolescents in the SUD group had lower scores on Attention, Memory, and Processing Speed composites, and FHP adolescents had poorer Visuospatial Ability. Conclusions: In combination, these analyses suggest that heavy alcohol use in adolescence leads to reduction in attention and executive functioning and that marijuana use exerts an independent deleterious effect on memory. At the same time, premorbid deficits associated with family history of AUD appeared to be specific to visuospatial ability.     

Brain diffusion abnormalities in children with fetal alcohol spectrum disorder

Background: Children with fetal alcohol spectrum disorder (FASD) have a variety of cognitive, behavioral, and neurological impairments, including structural brain damage. Despite the importance of white matter connections for proper brain function, little is known about how these connections, and the deep gray matter structures that act as relay stations, are affected in children with FASD. The purpose of this study was to use diffusion tensor imaging, an advanced magnetic resonance imaging technique, to examine microstructural differences of white and deep gray matter in children with FASD. Methods: Subjects were 24 children aged 5–13 years previously diagnosed with FASD and 95 healthy children over the same age range. Diffusion tractography was used to delineate 10 major white matter tracts in each individual, and region‐of‐interest analysis was used to assess 4 deep gray matter structures. Fractional anisotropy, an indicator of white matter integrity, and mean diffusivity, a measure of the average water diffusion, were assessed in all 14 brain structures. Results: Diffusion tensor imaging revealed significant differences of diffusion parameters in several areas of the brain, including the genu and splenium of the corpus callosum, cingulum, corticospinal tracts, inferior fronto‐occipital fasciculus, inferior and superior longitudinal fasciculi, globus pallidus, putamen, and thalamus. Reduced white and gray matter volumes, as well as total brain volume, were observed in the FASD group. Conclusions: These results demonstrate diffusion abnormalities in FASD beyond the corpus callosum and suggest that several specific white matter regions, particularly commissural and temporal connections, and deep gray matter areas of the brain are sensitive to prenatal alcohol exposure.     

Inter-hemispheric functional connectivity disruption in children with prenatal alcohol exposure

Background: MRI studies, including recent diffusion tensor imaging (DTI) studies, have shown corpus callosum abnormalities in children prenatally exposed to alcohol, especially in the posterior regions. These abnormalities appear across the range of fetal alcohol spectrum disorders (FASD). Several studies have demonstrated cognitive correlates of callosal abnormalities in FASD including deficits in visual‐motor skill, verbal learning, and executive functioning. The goal of this study was to determine whether inter‐hemispheric structural connectivity abnormalities in FASD are associated with disrupted inter‐hemispheric functional connectivity and disrupted cognition. Methods: Twenty‐one children with FASD and 23 matched controls underwent a 6‐minute resting‐state functional MRI scan as well as anatomical imaging and DTI. Using a semi‐automated method, we parsed the corpus callosum and delineated 7 inter‐hemispheric white matter tracts with DTI tractography. Cortical regions of interest (ROIs) at the distal ends of these tracts were identified. Right–left correlations in resting fMRI signal were computed for these sets of ROIs, and group comparisons were made. Correlations with facial dysmorphology, cognition, and DTI measures were computed. Results: A significant group difference in inter‐hemispheric functional connectivity was seen in a posterior set of ROIs, the para‐central region. Children with FASD had functional connectivity that was 12% lower than in controls in this region. Subgroup analyses were not possible owing to small sample size, but the data suggest that there were effects across the FASD spectrum. No significant association with facial dysmorphology was found. Para‐central functional connectivity was significantly correlated with DTI mean diffusivity, a measure of microstructural integrity, in posterior callosal tracts in controls but not in FASD. Significant correlations were seen between these structural and functional measures, and Wechsler perceptual reasoning ability. Conclusions: Inter‐hemispheric functional connectivity disturbances were observed in children with FASD relative to controls. The disruption was measured in medial parietal regions (para‐central) that are connected by posterior callosal fiber projections. We have previously shown microstructural abnormalities in these same posterior callosal regions, and the current study suggests a possible relationship between the two. These measures have clinical relevance as they are associated with cognitive functioning.     

Attention-deficit/hyperactivity disorder risk for heavy drinking and alcohol use disorder is age specific

BACKGROUND: This study was designed to assess age specificity in the risk for heavy drinking and alcohol use disorder (AUD) among adolescents and young adults with Attention-Deficit/Hyperactivity Disorder (ADHD) diagnosed in childhood. METHOD: Children diagnosed with ADHD (n=364 probands) were interviewed an average of 8 years later in the Pittsburgh ADHD Longitudinal Study, either as adolescents (11-17 years old) or as young adults (18-28 years of age). Demographically similar age-matched participants without ADHD were recruited as adolescents (n=120) or as adults (n=120) for comparison with the probands. Alcohol involvement was assessed comprehensively to include measures of heavy drinking that are standard in alcoholism research and prognostic of later alcohol-related problems. RESULTS: Results revealed age specificity in the association such that episodic heavy drinking (measured as 5+ drinks per occasion), drunkenness, DSM-IV AUD symptoms, and DSM-IV AUD were elevated among 15- to 17-year-old probands, but not among younger adolescents. Among young adults, drinking quantity and AUD were elevated among probands with antisocial personality disorder. Childhood predictors indexing antisocial behavior were also examined. CONCLUSIONS: The age- specificity of these findings helps to explain prior inconsistencies across previous studies regarding risk for alcohol-related outcomes among children with ADHD.