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.

Decreased frontal N-acetylaspartate levels in adolescents concurrently using both methamphetamine and marijuana.

INTRODUCTION: The potential neurochemical toxicity associated with methamphetamine (MA) or marijuana (MJ) use on the developing adolescent brain is unclear, particularly with regard to individuals with concomitant use of MA and MJ (MA+MJ). In this study, proton magnetic resonance spectroscopy (MRS) was utilized to measure in vivo brain N-acetylaspartate plus N-acetylaspartyl glutamate (tNAA, an indicator of intact neuronal integrity) levels. METHODS: Three adolescent groups from Cape Town, South Africa completed MRS scans as well as clinical measures including a drug use history. Subjects included (1) nine MA (age=15.7±1.37), (2) eight MA+MJ (age=16.2±1.16) using adolescents and (3) ten healthy controls (age=16.8±0.62). Single voxel spectra were acquired from midfrontal gray matter using a point-resolved spectroscopy sequence (PRESS). The MRS data were post-processed in the fully automated approach for quantitation of metabolite ratios to phosphocreatine plus creatine (PCr+Cr). RESULTS: A significant reduction in frontal tNAA/PCr+Cr ratios was seen in the MA+MJ group compared to the healthy controls (p=0.01, by 7.2%) and to the MA group (p=0.04, by 6.9%). Significant relationships were also observed between decreased tNAA/PCr+Cr ratios and drug use history of MA or MJ (total cumulative lifetime dose, age of onset, and duration of MA and MJ exposure) only in the MA+MJ group (all p<0.05). CONCLUSIONS: These findings suggest that in adolescents, concomitant heavy MA+MJ use may contribute to altered brain metabolites in frontal gray matter. The significant associations between the abnormal tNAA/PCr+Cr ratios and the drug use history suggest that MA+MJ abuse may induce neurotoxicity in a dose-responsive manner in adolescent brain.

Relationship between neurocognition and regional brain volumes in traumatized adolescents with and without posttraumatic stress disorder.

OBJECTIVES: Studies using convergent neurocognitive and structural imaging paradigms in adolescent posttraumatic stress disorder (PTSD) are limited; in the current study we used both voxel-based morphometry (VBM) to obtain between-group volumetric differences, and Freesurfer to examine the relationship between cognition and regional brain volumes. METHODS: Participants were 21 traumatized adolescents with PTSD matched with 32 traumatized adolescents without PTSD. Magnetic resonance images were obtained on a 1.5-Tesla MAGNETOM Siemens Symphony scanner. VBM implemented on FSL was then used to compare between-group grey matter volumes, after which Freesurfer was used to obtain global volume and thickness measurements in different brain regions. RESULTS: Significant between-group neurocognitive differences were found for tests of attention, delayed recall and visual reconstruction. On VBM, reduced grey matter was found in three regions in the PTSD group: left insula, right precuneus and right cingulate gyrus, using uncorrected values (p < 0.001), while no statistically significant between-group differences were found on the initial Freesurfer stream. Further Freesurfer analysis on Qdec revealed significant reductions in the insula for the PTSD group. In addition, volumetric changes in the corpus callosum and insula were significantly associated with deficits in logical memory and visual reproduction on Freesurfer analysis. CONCLUSIONS: Trauma exposure of itself may be sufficient to cause structural changes in adolescents regardless of PTSD development.

Abnormal striatal circuitry and intensified novelty seeking among adolescents who abuse methamphetamine and cannabis.

It has been hypothesized that changes in striatal-mediated dopamine modulation during adolescence may increase the risk for initiating substance abuse as a result of its fundamental role in arbitrating reward sensitivity and motivation during learning and decision making. However, substance abuse during adolescence may also significantly modify striatal structure and function and concomitantly alter reward sensitivity and action control while this brain region is undergoing remodeling. In the present investigation, to assess the relationship of methamphetamine (Meth) or Meth and cannabis (CA) abuse to regional striatal morphology, we acquired structural magnetic resonance images, using a 3T Siemens Trio scanner, from three groups of adolescents composed of healthy controls (n = 10), Meth abusers (n = 9) and combined Meth and CA abusers (Meth+CA, n = 8). We also assessed novelty seeking using the novelty seeking subscale of Cloninger's Tridimensional Character Inventory. The results indicate that adolescent Meth+CA abusers have increased regional striatal volume and show intensified novelty seeking in contrast to the controls. The degree of Meth exposure was also positively correlated with regional striatal volume and novelty seeking in both the Meth and Meth+CA users. These preliminary findings support theories that propose a role for the striatum in adolescent substance abuse and further indicate that novelty seeking may be related to the initiation of, or sustained, drug use.

Vitamin D and calcium status in South African adolescents with alcohol use disorders.

Adequate vitamin D and calcium are essential for optimal adolescent skeletal development. Adolescent vitamin D insufficiency/deficiency and poor calcium intake have been reported worldwide. Heavy alcohol use impacts negatively on skeletal health, which is concerning since heavy adolescent drinking is a rising public health problem. This study aimed to examine biochemical vitamin D status and dietary intakes of calcium and vitamin D in 12-16 year-old adolescents with alcohol use disorders (AUD), but without co-morbid substance use disorders, compared to adolescents without AUD. Substance use, serum 25-hydroxyvitamin D (s-25(OH)D) concentrations, energy, calcium and vitamin D intakes were assessed in heavy drinkers (meeting DSM-IV criteria for AUD) (n = 81) and in light/non-drinkers without AUD (non-AUD) (n = 81), matched for age, gender, language, socio-economic status and education. Lifetime alcohol dose was orders of magnitude higher in AUD adolescents compared to non-AUD adolescents. AUD adolescents had a binge drinking pattern and "weekends-only" style of alcohol consumption. Significantly lower (p = 0.038) s-25(OH)D (adjusted for gender, smoking, vitamin D intake) were evident in AUD adolescents compared to non-AUD adolescents. High levels of vitamin D insufficiency/deficiency (s-25(OH)D < 29.9 ng/mL) were prevalent in both groups, but was significantly higher (p = 0.013) in the AUD group (90%) compared to the non-AUD group (70%). All participants were at risk of inadequate calcium and vitamin D intakes (Estimated Average Requirement cut-point method). Both groups were at risk of inadequate calcium intake and had poor biochemical vitamin D status, with binge drinking potentially increasing the risk of the latter. This may have negative implications for peak bone mass accrual and future osteoporosis risk, particularly with protracted binge drinking.

Quetiapine augmentation of serotonin reuptake inhibitors in treatment-refractory obsessive-compulsive disorder: is response to treatment predictable?

Several studies have examined the predictors of treatment response in obsessive-compulsive disorder (OCD). Only limited information is available on the predictors of response to antipsychotic augmentation of serotonin reuptake inhibitors (SRIs). Data from placebo-controlled studies of augmentation with quetiapine were combined in a best subsets logistic regression to derive a predictive model for Yale-Brown obsessive-compulsive scale (YBOCS) change and the YBOCS endpoint. Data from the YBOCS checklist and a variety of clinical and demographic variables previously shown to predict treatment outcome in OCD were analysed. In univariate analyses, the failure of fewer previous SRI trials was associated with the YBOCS response. In the multivariate model, for YBOCS change, 45% of the variance was attributed to the fact that patients had failed fewer previous SRI treatments, had higher baseline obsession scores, and ordering and arranging compulsions. For the YBOCS endpoint scores, 50% of the variance was attributed to the fact that patients had fewer failed SRI trials, higher baseline compulsion scores, and counting/ordering and arranging compulsions. These data indicate a number of predictors of response to augmentation of SRIs in treatment-refractory OCD. These include fewer previously failed SRI trials and generally higher overall baseline scores for obsessions and compulsions as well as counting/ordering and arranging compulsions. Other factors are, however, also likely to play an important role in predicting outcome.

Grey matter abnormalities in social anxiety disorder: a pilot study.

While a number of studies have explored the functional neuroanatomy of social anxiety disorder (SAD), data on grey matter integrity are lacking. We conducted structural MRI scans to examine the cortical thickness of grey matter in individuals with SAD. 13 unmedicated adult patients with a primary diagnosis of generalized social anxiety disorder and 13 demographically (age, gender and education) matched healthy controls underwent 3T structural magnetic resonance imaging. Cortical thickness and subcortical volumes were estimated using an automated algorithm (Freesurfer Version 4.5). Compared to controls, social anxiety disorder patients showed significant bilateral cortical thinning in the fusiform and post central regions. Additionally, right hemisphere specific thinning was found in the frontal, temporal, parietal and insular cortices of individuals with social anxiety disorder. Although uncorrected cortical grey matter volumes were significantly lower in individuals with SAD, we did not detect volumetric differences in corrected amygdala, hippocampal or cortical grey matter volumes across study groups. Structural differences in grey matter thickness between SAD patients and controls highlight the diffuse neuroanatomical networks involved in both social anxiety and social behavior. Additional work is needed to investigate the causal mechanisms involved in such structural abnormalities in SAD.

Growth and weight status in treatment-naïve 12-16 year old adolescents with alcohol use disorders in Cape Town, South Africa.

BACKGROUND: Heavy alcohol consumption during adolescence has many known harmful health and social consequences and is strongly associated with numerous health risk behaviours. The consequences of heavy alcohol use during adolescence on nutritional status, specifically growth and weight status are largely unknown at this time. METHODS: Substance use, anthropometric indices of growth and weight, dietary energy intake and physical activity in heavy drinking adolescents (meeting DSM-IV criteria for alcohol use disorders) and matched light/non-drinking control adolescents were assessed. RESULTS: Lifetime alcohol dose, measured in standard drinks of alcohol, was orders of magnitude higher in adolescents with alcohol use disorders (AUDs) compared to controls. The AUDs group was selected to represent relatively 'pure' AUDs, with minimal other drug use and no psychiatric diagnoses. The growth and weight status of adolescents with AUDs were generally comparable to that of controls, and is in line with the growth and weight status of the South African adolescent population. A greater proportion of overweight/obese females was found in both groups, with this percentage tending to be greater, although not significantly so, in the AUDs group. Adolescent females with AUDs had increased odds of being overweight/obese compared to controls, after adjustment for smoking, physical activity and energy intake. CONCLUSION: Anthropometric indices of growth and weight status of participants in the Control and AUD groups were generally comparable. Female adolescents with AUDs may have an increased risk of being overweight/obese compared to adolescent females without AUDs. The presence of an AUD in our adolescent sample was associated with higher energy intake. Longitudinal studies are needed to elucidate the effects of heavy alcohol use on energy balance, growth and weight status in adolescents as they age. Nonetheless, the current study contributes to our understanding of the impacts of heavy alcohol consumption on important aspects of adolescent development.

Lymphocyte measures in treatment-naïve 13-15-year old adolescents with alcohol use disorders.

Many adolescents have chronic exposure to hazardous levels of alcohol. This is likely to be a significant predictor of health outcomes, including those related to immunity. We assessed substance use and biochemical immunological parameters in heavy drinking adolescents (meeting DSM-IV criteria for alcohol dependence) and light/nondrinking control adolescents in Cape Town. Lifetime alcohol dose, measured in standard units of alcohol, was orders of magnitude higher in alcohol-dependent (AD) participants than controls. All adolescent AD had a "weekends-only" style of alcohol consumption. The AD group was chosen to represent relatively "pure" AD, with minimal other drug use and no psychiatric diagnoses. With these narrow parameters in place, we found that AD adolescents were lymphopenic compared with controls, with significantly lower mean numbers of absolute circulating CD3+, CD4+, and CD8+ T-lymphocytes. On conclusion, we found that adolescent AD individuals with excessive alcohol intake, in a weekend binge-drinking style but without comorbid drug or psychiatric disorders, may be at increased risk of lymphopenia. This alcohol misuse may increase infectious disease susceptibility (including TB and HIV) by reducing immune system capabilities. Complex interactions of alcohol with other documented high-risk activities may further compound health risks.

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.

Changes in regional brain volumes in social anxiety disorder following 12 weeks of treatment with escitalopram.

It has been suggested that antidepressants, including the selective serotonin reuptake inhibitors have neurotrophic effects. Nevertheless, the impact of treatment with a selective serotonin re-uptake inhibitor on regional brain volumes in social anxiety disorder has not been studied. 11 subjects with social anxiety disorder completed magnetic resonance imaging both before and after 12-weeks of treatment with 20 mg/day escitalopram. No increases in structural grey matter were found, but there were decreases in bilateral superior temporal cortex, vermis and the left cerebellum volumes following 12 weeks of treatment with escitalopram. These preliminary findings require replication to determine their reliability, and extension to determine whether or not they are disorder specific.

White matter correlates of apathy in HIV-positive subjects: a diffusion tensor imaging study.

Apathy is commonly reported by patients infected with HIV. No previous work has assessed the relationship between white matter and apathy in HIV. The authors aimed to determine whether apathy in HIV reflects a direct effect of the virus on subcortical brain regions or a secondary neuropsychiatric symptom. Thirteen HIV+ participants with apathy, 13 HIV+ participants with no apathy, and 10 healthy comparison subjects were examined using diffusion tensor imaging in the region of the anterior cingulate and corpus callosum. Results of the study confirmed the hypothesis which anticipated changes associated with apathy in white matter tracts that relay through the medial prefrontal cortex.

Neuropsychological performance of South African treatment-naïve adolescents with alcohol dependence.

BACKGROUND: Alcohol dependence (AD) in developmentally vulnerable adolescents is ubiquitous and confers a risk for long-term neurocognitive sequelae, yet comorbid substance use disorders and psychopathology can complicate interpretations. Here, we compare cognitive functioning in adolescents with and without AD, who are free from comorbid disorders. METHODS: English- and Afrikaans-speaking adolescents (13-15 years) of mixed ancestry and low socio-economic status were recruited from the Cape Town region of South Africa. Adolescents with psychiatric, developmental, or other substance use disorders (SUDs) were excluded. AD (n=26) and control (n=26) groups were matched on age, gender, language, and level of education. Neuropsychological testing in participants' home language followed detailed medical/psychiatric evaluation. RESULTS: Although our sample included participants who smoked tobacco, lifetime dosage of other drugs was negligible. When tobacco and other drug use as well as demographic variables were controlled, adolescents with AD performed more poorly on measures of Verbal Story Memory, Self-Monitoring, and Psychomotor Speed and Coordination. CONCLUSIONS: These preliminary results, although relatively subtle, suggest that adolescents with AD may be at increased risk for failure to reach optimal levels of neuromaturation, and may be susceptible to cognitive problems associated with protracted alcohol consumption.

The role of the brain-derived neurotrophic factor (BDNF) val66met variant in the phenotypic expression of obsessive-compulsive disorder (OCD).

Evidence suggests that the Val66Met variant of the brain-derived neurotrophic factor (BDNF) gene may play a role in the etiology of Obsessive-Compulsive Disorder (OCD). In this study, the role of the BDNF Val66Met variant in the etiology and the phenotypic expression of OCD is investigated. Associations between the BDNF Val66Met variant and OCD, obsessive-compulsive symptom dimensions, Yale-Brown Obsessive Compulsive Scale (YBOCS) severity scores, age of onset and family history of obsessive-compulsive symptoms were assessed. The BDNF Val66Met variant was genotyped in 419 patients with sub-/clinical OCD and 650 controls. No differences in allele or genotype frequency were observed between cases and controls. In females with OCD, the Met66Met genotype was associated with later age of onset and a trend for a negative family history, whereas the Val66Val genotype was associated with a trend for lower YBOCS severity scores. Item-level factor analysis revealed six factors: 1) Contamination/cleaning; 2) Aggressive obsessions/checking; 3) Symmetry obsessions, counting, ordering and repeating; 4) Sexual/religious obsessions; 5) Hoarding and 6) Somatic obsessions/checking. A trend was found for a positive association between Factor 4 (Sexual/religious obsessions) and the BDNF Val66Val genotype. The results suggest that BDNF function may be implicated in the mediation of OCD. We found that for the BDNF Met66Met genotype may be associated with a milder phenotype in females and a possible role for the BDNF Val66Val genotype and the BDNF Val66 allele in the sexual/religious obsessions.

Escitalopram in obsessive-compulsive disorder: response of symptom dimensions to pharmacotherapy.

INTRODUCTION: There is a substantial body of evidence that obsessive-compulsive disorder (OCD) symptoms can be grouped into a series of discrete dimensions, and some evidence that not all OCD symptom dimensions respond equally well to pharmacologic or psychotherapeutic intervention. The response of OCD symptom dimensions to 12 weeks of treatment with escitalopram or placebo was investigated. METHODS: Data from a randomized, double-blind, placebo-controlled study of escitalopram in 466 adults with OCD were analyzed. Exploratory factor analysis of individual items of the Yale-Brown Obsessive-Compulsive Scale checklist was performed and subscale scores based on the extracted factors were determined. Analyses of covariance were undertaken to determine whether inclusion of each subscale score in these models impacted on the efficacy of escitalopram versus placebo. RESULTS: Exploratory factor analysis of individual Yale-Brown Obsessive-Compulsive Scale items yielded 5 factors (contamination/cleaning, harm/checking, hoarding/symmetry, religious/sexual, and somatic/hypochondriacal). Analyses of covariance including all the subscales demonstrated that escitalopram was more effective than placebo. There was a significant interaction for the hoarding/symmetry factor, which was associated with a poor treatment response. CONCLUSION: Escitalopram shows good efficacy across the range of OCD symptom dimensions. Nevertheless, hoarding/symmetry was associated with a poorer treatment response. Hoarding/symmetry may be particularly characteristic of an early-onset group of OCD patients, with the involvement of neurotransmitters other than serotonin. Further work is needed to delineate fully the subtypes of OCD, and their correlates with underlying psychobiology and treatment responsivity.

Risk indicators and psychopathology in traumatised children and adolescents with a history of sexual abuse.

PURPOSE: Childhood sexual abuse (CSA) is widespread amongst South African (SA) children, yet data on risk factors and psychiatric consequences are limited and mixed. METHODS: Traumatised children and adolescents referred to our Youth Stress Clinic were interviewed to obtain demographic, sexual abuse, lifetime trauma and psychiatric histories. RESULTS: Data for 94 participants (59 female, 35 male; mean age 14.25 [8.25-19] years) exposed to at least one lifetime trauma were analysed. Sexual abuse was reported in 53% of participants (42.56% females, 10.63% males) with 64% of violations committed by perpetrators known to them. Multinomial logistic regression analysis revealed female gender (P=0.002) and single-parent families (P=0.01) to be significant predictors of CSA (62.5%). CSA did not predict exposure to other traumas. Sexually abused children had significantly higher physical and emotional abuse subscale scores and total CTQ scores than non-abused children. Depression (33%, X(2)=10.89, P=0.001) and PTSD (63.8%, X(2)=4.79, P=0.034) were the most prevalent psychological consequences of trauma and both were significantly associated with CSA. CONCLUSIONS: High rates of CSA predicted high rates of PTSD in this traumatised sample. Associations we found appear consistent with international studies of CSA and, should be used to focus future social awareness, prevention and treatment strategies in developing countries.

Quetiapine addition in obsessive-compulsive disorder: is treatment outcome affected by type and dose of serotonin reuptake inhibitors?

BACKGROUND: The purpose of this study was to assess the effect of type and dose of serotonin reuptake inhibitors (SRIs) on treatment outcome in quetiapine addition trials for obsessive-compulsive disorder. METHODS: Results from all available, double blind, placebo-controlled quetiapine addition trials were pooled. Treatment outcome was assessed in a sample of 102 patients by change from baseline to end point on the Yale-Brown obsessive-compulsive scale (Y-BOCS). RESULTS: Quetiapine addition was superior with a mean Y-BOCS decrease of 6.8 +/- 6.7 compared with placebo with a decrease of 3.9 +/- 6.5 points. Patients with the lowest SRI dose showed the largest decrease on the Y-BOCS (11.6 +/- 7.7) compared with patients with the median dose (6.1 +/- 6.1) and highest dose (5.9 +/- 6.4). CONCLUSIONS: We found a superior response in the quetiapine addition group compared with the placebo group. The best response was achieved with the combination of clomipramine, fluoxetine, and fluvoxamine and with the lowest SRI doses.

Beauty and the beast: Psychobiologic and evolutionary perspectives on body dysmorphic disorder.

Body dysmorphic disorder (BDD) is characterized by preoccupation with a defect in appearance. Concepts of beauty play a particularly crucial role in humans' mental and social life, and may have specific psychobiologic and evolutionary underpinnings. In particular, there is a growing literature on the neurocircuitry underpinning the body schema, body image and facial expression processing, and aesthetic and symmetry judgments. Speculatively, disruptions in cognitive-affective processes relevant to judgements about physical beauty lead to BDD.