Sex differences in associations between white matter microstructure and gonadal hormones in children and adolescents with prenatal alcohol exposure.

Despite accumulating evidence from animal models demonstrating that prenatal alcohol exposure (PAE) results in life-long neuroendocrine dysregulation, very little is known on this topic among humans with fetal alcohol spectrum disorders (FASD). We expected that alterations in gonadal hormones might interfere with the typical development of white matter (WM) myelination, and in a sex-dependent manner, in human adolescents with FASD. In order to investigate this hypothesis, we used diffusion tensor imaging (DTI) to assess: 1) whether or not sex moderates the impact of PAE on WM microstructure; and 2) how gonadal hormones relate to alterations in WM microstructure in children and adolescents affected by PAE. METHODS: 61 youth (9 to 16 yrs.; 49% girls; 50% PAE) participated as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD). DTI scans and passive drool samples were obtained to examine neurodevelopmental associations with testosterone (T) and dehydroepiandrosterone (DHEA) levels in boys and girls, and estradiol (E2) and progesterone (P) levels in girls. Tract-based spatial statistics were utilized to generate fractional anisotropy (FA) and mean diffusivity (MD) for 9 a priori WM regions of interest (ROIs). RESULTS: As predicted, alterations in FA were observed in adolescents with PAE relative to controls, and these differences varied by sex. Girls with PAE exhibited lower FA (Inferior fronto-occipital and Uncinate fasciculi) while boys with PAE exhibited higher FA (Callosal body, Cingulum, Corticospinal tract, Optic radiation, Superior longitudinal fasciculus) relative to age-matched controls. When gonadal hormone levels were examined in relation to DTI measures, additional group differences in FA were revealed, demonstrating that neuroendocrine factors are associated with PAE-related brain alterations. CONCLUSIONS: These findings provide human evidence that PAE relates to sex-specific differences in WM microstructure, and underlying alterations in gonadal hormone function may, in part, contribute to these effects. Determining PAE-effects on neuroendocrine function among humans is an essential first step towards developing novel clinical (e.g., assessment or intervention) tools that target hormone systems to improve on-going brain development among children and adolescents with FASD.

Clonidine for sleep disturbances associated with attention-deficit hyperactivity disorder: a systematic chart review of 62 cases.

OBJECTIVE: Children and adolescents with attention-deficit hyperactivity disorder (ADHD), with or without psychostimulant treatment, frequently suffer from sleep disturbances. This report evaluates the use of clonidine in the treatment of sleep disturbances associated with ADHD. METHOD: A systematic search of a computerized database in an outpatient pediatric psychopharmacology unit of patients treated with clonidine for ADHD-associated sleep disturbances (N = 62; 42 children and 20 adolescents) was performed. Patients were rated retrospectively about the type and severity of sleep disturbances at baseline and after treatment with clonidine. RESULTS: A majority of patients (85%) treated with clonidine for ADHD-associated sleep disturbances were considered to be much to very much improved by the National Institute of Mental Health global assessment of improvement (sleep). Nighttime clonidine doses ranged from 50 to 800 micrograms (mean +/- SEM; 157 +/- 14 micrograms), and subjects received clonidine for 35.5 +/- 3.5 months. There was no association between response and age group, gender, comorbidity, or concurrent pharmacotherapy. Children and adolescents with ADHD with baseline, medicine-induced, or medicine-exacerbated sleep disturbances responded equally well to clonidine treatment. Mild adverse effects were reported in 19 subjects (31%). CONCLUSIONS: These findings suggest that clonidine may be an effective agent for sleep disturbances associated with ADHD, or its treatment, and warrant further controlled investigations.