White matter fiber bundle lengths are shorter in cART naive HIV: an analysis of quantitative diffusion tractography in South Africa.

This study examines white matter microstructure using quantitative tractography diffusion magnetic resonance imaging (qtdMRI) in HIV+ individuals from South Africa who were naïve or early in the initiation of antiretroviral therapy. Fiber bundle length (FBL) metrics, generated from qtdMRI, for whole brain and six white matter tracts of interest (TOI) were assessed for 135 HIV+ and 21 HIV- individuals. The association between FBL metrics, measures of disease burden, and neuropsychological performance were also investigated. Results indicate significantly reduced sum of whole brain fiber bundle lengths (FBL, p < 0.001), but not average whole brain FBL in the HIV+ group compared to the HIV- controls. The HIV+ group exhibited significantly shorter sum of FBL in all six TOIs examined: the anterior thalamic radiation, cingulum bundle, inferior and superior longitudinal fasciculi, inferior frontal occipital fasciculus, and the uncinate fasciculus. Additionally, average FBLs were significantly shorter select TOIs including the inferior longitudinal fasciculus, cingulum bundle, and the anterior thalamic radiation. Shorter whole brain FBL sum metrics were associated with poorer neuropsychological performance, but were not associated with markers of disease burden. Taken together these findings suggest HIV affects white matter architecture primarily through reductions in white matter fiber numbers and, to a lesser degree, the shortening of fibers along a bundle path.

Familial influences on the full range of variability in attention and activity levels during adolescence: A longitudinal twin study.

To investigate familial influences on the full range of variability in attention and activity across adolescence, we collected maternal ratings of 339 twin pairs at ages 12, 14, and 16, and estimated the transmitted and new familial influences on attention and activity as measured by the Strengths and Weaknesses of Attention-Deficit/Hyperactivity Disorder Symptoms and Normal Behavior Scale. Familial influences were substantial for both traits across adolescence: genetic influences accounted for 54%-73% (attention) and 31%-73% (activity) of the total variance, and shared environmental influences accounted for 0%-22% of the attention variance and 13%-57% of the activity variance. The longitudinal stability of individual differences in attention and activity was largely accounted for by familial influences transmitted from previous ages. Innovations over adolescence were also partially attributable to familial influences. Studying the full range of variability in attention and activity may facilitate our understanding of attention-deficit/hyperactivity disorder's etiology and intervention.

Revising the BIS/BAS Scale to study development: Measurement invariance and normative effects of age and sex from childhood through adulthood.

Carver and White's (1994) Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) Scales have been useful tools for studying individual differences in reward-punishment sensitivity; however, their factor structure and invariance across development have not been well tested. In the current study, we examined the factor structure of the BIS/BAS Scales across 5 age groups: 6- to 10-year-old children (N = 229), 11- to 13-year-old early adolescents (N = 311), 14- to 16-year-old late adolescents (N = 353), 18- to 22-year-old young adults (N = 844), and 30- to 45-year-old adults (N = 471). Given poor fit of the standard 4-factor model (BIS, Reward Responsivity, Drive, Fun Seeking) in the literature, we conducted exploratory factor analyses in half of the participants and identified problematic items across age groups. The 4-factor model showed poor fit in our sample, whereas removing the BAS Fun Seeking subscale and problematic items from the remaining subscales improved fit in confirmatory factor analyses conducted with the second half of the participants. The revised model showed strict invariance across age groups and by sex, indicating consistent factor structure, item loadings, thresholds, and unique or residual variances. Additionally, in our cross-sectional data, we observed nonlinear relations between age and subscale scores, where scores tended to be higher in young adulthood than in childhood and later adulthood. Furthermore, sex differences emerged across development; adolescent and adult females had higher BIS scores than males in this age range, whereas sex differences were not observed in childhood. These differences may help us to understand the rise in internalizing psychopathology in adolescence, particularly in females. Future developmental studies are warranted to examine the impact of rewording problematic items.

Activity-dependent regulation of release probability at excitatory hippocampal synapses: a crucial role of fragile X mental retardation protein in neurotransmission.

Transcriptional silencing of the Fmr1 gene encoding fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS), the most common form of inherited intellectual disability and the leading genetic cause of autism. FMRP has been suggested to play important roles in regulating neurotransmission and short-term synaptic plasticity at excitatory hippocampal and cortical synapses. However, the origins and mechanisms of these FMRP actions remain incompletely understood, and the role of FMRP in regulating synaptic release probability and presynaptic function remains debated. Here we used variance-mean analysis and peak-scaled nonstationary variance analysis to examine changes in both presynaptic and postsynaptic parameters during repetitive activity at excitatory CA3-CA1 hippocampal synapses in a mouse model of FXS. Our analyses revealed that loss of FMRP did not affect the basal release probability or basal synaptic transmission, but caused an abnormally elevated release probability specifically during repetitive activity. These abnormalities were not accompanied by changes in excitatory postsynaptic current kinetics, quantal size or postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor conductance. Our results thus indicate that FMRP regulates neurotransmission at excitatory hippocampal synapses specifically during repetitive activity via modulation of release probability in a presynaptic manner. Our study suggests that FMRP function in regulating neurotransmitter release is an activity-dependent phenomenon that may contribute to the pathophysiology of FXS.

Gender differences in the factor structure of the Alcohol Use Disorders Identification Test in multinational general population surveys.

BACKGROUND: Most gender-specific studies of the Alcohol Use Disorders Identification Test (AUDIT) have focused on gender differences in thresholds for hazardous drinking. This study examines gender differences in the factor structure of the AUDIT in general-population surveys. METHODS: General-population surveys from 15 countries provided 27,478 current drinkers' responses to the AUDIT and related measures. We used single-group confirmatory factor analysis (CFA) to evaluate goodness-of-fit of three hypothesized models for responses to the AUDIT by men and women in each country. Bayesian Information Criteria (BIC) using a maximum likelihood robust (MLR) estimator was evaluated to identify the best fitted model. We then assessed factorial invariance within country surveys where fit indices were acceptable for both genders. Gender-specific internal consistency and concurrent validity were also evaluated in all 15 countries. RESULTS: CFA revealed that the fit indices of 2-factor or 3-factor models were consistently better than fit indices for a 1-factor model in 14 of 15 countries. Comparisons of BIC values indicated that the 2-factor solution was the best fitted model. Factorial invariance tests in data from 3 countries indicated that the factor loadings and thresholds of the AUDIT were invariant across gender. The internal reliability and concurrent validity of AUDIT and its subscales were acceptable in both genders. CONCLUSIONS: A two-factor model best describes AUDIT responses across general-population surveys in 12 of 15 countries, with acceptable internal reliability and concurrent validity, and supports a gender-invariant structure in at least three of those countries.

Fetal alcohol spectrum disorders: a population based study of premature mortality rates in the mothers.

Fetal alcohol spectrum disorders (FASD) are associated with an increase in risk for mortality for people with an FASD and their siblings. In this study we examine mortality rates of birth mothers of children with FASD, using a retrospective case control methodology. We utilized the North Dakota FASD Registry to locate birth certificates for children with FASD which we used to identify birth mothers. We then searched for mothers' death certificates. We then compared the mortality rates of the birth mothers with an age matched control group comprised of all North Dakota women who were born and died in the same year as the birth mother. The birth mothers of children with FASD had a mortality rate of 15/304 = 4.93%; (95% CI 2.44-7.43%). The mortality rate for control mothers born in same years as the FASD mothers was 126/114,714 = 0.11% (95% CI 0.09-0.13%). Mothers of children with an FASD had a 44.82 fold increase in mortality risk and 87% of the deaths occurred in women under the age of 50. Three causes of death (cancer, injuries, and alcohol related disease) accounted for 67% of the deaths in the mothers of children with FASD. A diagnosis of FASD is an important risk marker for premature death in the mothers of children diagnosed with an FASD. These women should be encouraged to enter substance abuse treatment.

Tourette syndrome and comorbid early-onset schizophrenia.

OBJECTIVE: A study of the shared phenomenology between Tourette syndrome (TS) and schizophrenia. METHOD: An illustrative case report is presented. We used a chart review of 399 clinically ascertained patients with TS to identify 10 cases meeting criteria for schizophrenia. From our 10 patients, salient clinical characteristics were then tabulated. We then extracted similar clinical characteristics from a previously published series of patients with comorbid TS and schizophrenia in order to combine cases and allow for a comparison between childhood-onset schizophrenia (COS), adolescent-onset schizophrenia (AdolOS), and adult-onset schizophrenia (AduOS) cases in these groups. RESULTS: We found 10 cases of schizophrenia (all were males) in the 399 TS patients for a prevalence rate of 2.5% (95% CI 0.96-4.04). Mean age of tic onset for TS diagnostic criteria ranged from 2-14 years with a mean of 8.2 years. The mean age of diagnosis for schizophrenia was 14.2 (range 9-23 years). We found six cases of schizophrenia with onset of positive psychotic symptoms by 13 years of age, two cases with onset after 13 years of age and before 18 years of age, and two cases with onset after 18 years of age. Attention deficit hyperactivity disorder was present at a higher rate (70%) than one would expect in a clinically ascertained group of patients with TS. Comparison between COS, AdolOS and AduOS in our pooled cases noted a sex bias skewed toward males. Catatonic symptoms may be more likely in child or adolescent onset cases and negative symptoms more likely in AduOS cases. CONCLUSIONS: The 2.5% prevalence of schizophrenia in our TS sample exceeds the 1% expected rate of schizophrenia in the general population (chi-square=9.14; P=.0025). The six cases of COS (before 13 years of age) exceeds the expected rate of 1-2 per 100,000 (chi-square=4499; P=.0001). The 752-fold increase in observed rates of comorbid TS and COS over expected rates suggests a role for unknown common underlying etiologic factors. Based on clinical features, patients with TS and comorbid COS, AdolOS, or AduOS do not have different conditions. We conclude with suggestions for further research.

Health care costs and utilization rates for children with pervasive developmental disorders in North Dakota from 1998 to 2004: impact on Medicaid.

In this study, we used data from the North Dakota Medicaid claims database from 1998 through 2004 to estimate health care utilization rates and cost of care for children with pervasive developmental disorders. From the dataset, we developed a group comprised of children with pervasive developmental disorders (n = 546) and 2 comparison groups: children with other mental disorders (n = 18 363) and children who did not have pervasive developmental disorders or any mental disorders (n = 63 202). Participants with pervasive developmental disorders utilized 4.6% of all visits and 5% of the total cost of health care over the 7-year period. The average annual cost of care for children with pervasive developmental disorders was much higher than the cost for children without mental disorders for outpatient services ($5051 vs $360, ratio = 14:1), inpatient services ($1585 vs $458, ratio = 3.4:1), and pharmacy services ($1258 vs $82, ratio = 15:1). Children with pervasive developmental disorders covered by Medicaid have increased costs of health care.