Natalie L. Cuzen

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

Most prior studies of the effects of excessive alcohol intake on the adolescent brain examined alcohol-use-dependent samples with comorbid psychiatric and substance use disorders. In the Cape Town region, we identified a sizeable cohort of adolescents with alcohol use disorders (AUD) without externalizing or other psychiatric disorders. We examined brain morphology in 64 such adolescents compared to age- and gender-matched healthy controls. Magnetic resonance imaging data were analyzed using FSLs FIRST software for subcortical volumes, and cortical gray matter (GM) was analyzed using voxel-based morphometry (VBM) and regions of interest (ROI) analysis. AUD boys had smaller thalamic and putamen volumes compared to non-drinking boys, while AUD girls had larger thalamic and putamen volumes compared to non-drinking girls. VBM revealed a large region of decreased GM density in AUDs compared to controls located in the left lateral frontal, temporal, and parietal lobes, extending medially deep into the parietal lobe. Smaller GM volume in this region was also present when examined using ROI analysis. Our lack of findings in other brain regions, particularly the hippocampus, suggests that reports of smaller brain volumes in adolescent AUDs in the literature are a consequence of psychiatric and substance abuse comorbidities.

Comorbidity in obsessive-compulsive disorder (OCD): a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS).

BACKGROUND Obsessive-compulsive disorder (OCD) is often associated with significant psychiatric comorbidity. Comorbid disorders include mood and anxiety disorders as well as obsessive-compulsive spectrum disorders (OCSDs). This paper aims to investigate comorbidity of DSM Axis I-disorders, including OCSDs, in patients with OCD from 10 centers affiliated with the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS). METHODS This is a cross-sectional study of comorbidity of Axis I disorders including OCSDs in 457 outpatients with primary OCD (37% male; 63% female), with ages ranging from 12 to 88years (mean: 39.8±13). Treating clinicians assessed Axis I disorders using the Mini International Neuropsychiatric Interview and assessed OCSDs using the Structured Clinical Interview for OCD related/spectrum disorders (SCID-OCSD). RESULTS In terms of the OCSDs, highest comorbidity rates were found for tic disorder (12.5%), BDD (8.71%) and self-injurious behavior (7.43%). In terms of the other Axis I-disorders, major depressive disorder (MDD; 15%), social anxiety disorder (SAD; 14%), generalized anxiety disorder (GAD; 13%) and dysthymic disorder (13%) were most prevalent. DISCUSSION High comorbidity of some OCSDs in OCD supports the formal recognition of these conditions in a separate chapter of the nosology. Rates of other Axis I disorders are high in both the general population and in OCSDs, indicating that these may often also need to be the focus of intervention in OCD.

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

Objective The objective of this study is to examine white matter microstructure using diffusion tensor imaging (DTI) in a sample of adolescents with alcohol use disorders (AUD) and no psychiatric or substance co-morbidity. Methods Fifty adolescents with AUD and fifty non-alcohol abusing controls matched on gender and age were studied with DTI, neurocognitive testing, and a clinical assessment that included measures of alcohol use and childhood trauma. Maps of fractional anisotropy (FA) and mean diffusivity (MD) were computed, registered to a common template, and voxel-wise statistical analysis used to assess group differences. Associations between regions of altered WM microstructure and clinical or neurocognitive measures were also assessed. Results Compared with controls, adolescent drinkers without co-morbid substance abuse or externalizing disorder, showed 1) no regions of significantly lower FA, 2) increased FA in WM tracts of the limbic system; 3) no MD differences; and 4) within the region of higher FA in AUD, there were no associations between FA and alcohol use, cognition, or trauma. Discussion The most important observation of this study is our failure to observe significantly smaller FA in this relatively large alcohol abuse/dependent adolescent sample. Greater FA in the limbic regions observed in this study may index a risk for adolescent AUD instead of a consequence of drinking. Drinking behavior may be reinforced in those with higher FA and perhaps greater myelination in these brain regions involved in reward and reinforcement.

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.

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.

Methamphetamine and cannabis abuse in adolescence: a quasi-experimental study on specific and long-term neurocognitive effects

Objectives Methamphetamine abuse affects brain structure and function. Although methamphetamine and cannabis are commonly abused together, few studies have investigated the differential neurocognitive consequences of methamphetamine abuse with or without cannabis. Furthermore, the effects of drug use on the developing adolescent brain remain poorly understood. We compared neurocognitive function between adolescents with ‘pure’ methamphetamine abuse, those with comorbid methamphetamine and cannabis abuse, and healthy controls at baseline and follow-up. Methods Individuals residing in the greater Cape Town region, between the ages of 13 and 18 years, were recruited into either Methamphetamine only group (Meth-only; n=10), Methamphetamine and cannabis group (Meth-cann; n=10) or healthy control (n=20) groups using a quasi-experimental design. All participants underwent a comprehensive neurocognitive assessment. Substance-use variables and psychiatric symptom counts were also recorded. A portion of the Meth-only and control participants completed 12-month follow-up assessments. Results While the Meth-cann group demonstrated widespread neurocognitive deficits at baseline, these deficits were restricted to the self-monitoring domain in the Meth-only group at baseline and at follow-up. Conclusions Methamphetamine abuse with cannabis abuse is associated with significantly more neurocognitive impairment than methamphetamine abuse alone, and such deficits may be enduring.

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.

Comorbidity of obsessive-compulsive disorder and substance use disorder : A new heuristic

Obsessive–compulsive disorder (OCD) and substance use disorder share several aspects of phenomenology and may be underpinned by a common mechanism with compulsivity at the core. Despite this overlap, the two disorders show a variable pattern of comorbidity. Here, we review the current evidence for comorbidity across clinical and epidemiological studies, and propose a new heuristic for substance use comorbidity in OCD, based on a hypothetical threshold of OCD severity. Copyright

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.

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

BackgroundPrevious 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).MethodsWe 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.ResultsNo significant associations, corrected for multiple comparisons, were found between the BDNF p.Val66Met polymorphism, brain volumes and AUD in adolescents with childhood trauma.ConclusionsThese 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.