Luisa Lázaro

Predictors of bone mineral density reduction in adolescents with anorexia nervosa.

OBJECTIVES To determine which variables are associated with a significant reduction in bone mineral density (BMD) in adolescent anorexia nervosa and to establish guidelines for indication of bone densitometry. METHOD One hundred seventy patients (treated from 1997 until 1999), aged 10 to 17 years, with a DSM-IV diagnosis of anorexia nervosa were evaluated by dual-energy-x-ray absorptiometry in the lumbar spine (L2-L4) and the femoral neck. The results were compared with the normative data for BMD values by age and sex in Spanish adolescents. RESULTS 44.1% of patients had osteopenia at the lumbar spine and 24.7% at the femoral neck. The following variables were related to osteopenia: more than 12 months since onset of the disorder (p < .001), more than 6 months of amenorrhea (p < .001), body mass index <15 (p < .001), calcium intake <600 mg/day (p < .01), and <3 hours/week of physical activity (p < .001). In a stepwise logistic regression analysis to predict reduced spinal BMD, 3 variables-months elapsed since the onset of weight loss, calcium intake, and body mass index--correctly classified 78.8% of patients. CONCLUSIONS Adolescent anorexia nervosa patients with the characteristics outlined above are at high risk of reduced BMD, and densitometry is recommended to determine the degree of osteopenia.

Cognitive dysfunctions in recovered melancholic patients

Cognitive dysfunctions were studied in symptom-free patients suffering from Recurrent Depressive Disorder with melancholia. Their performances on a standard neuropsychological battery were compared with those of a healthy sample matched for age and educational level. Statistically significant differences were found in Immediate Visual Memory, Delayed Logical and Visual Memory, Paired Learning and Block Design. Results seem to indicate that the cognitive disfunctions are not likely to be only mnesic. All these data suggest that these disfunctions found in some melancholic depressives could not be state-dependent.

Neuropsychological Performance in Children and Adolescents with Obsessive-Compulsive Disorder and Influence of Clinical Variables

BACKGROUND Several studies have found impairment in visual memory and visual organization in adults with obsessive-compulsive disorder (OCD), but little is known about the neuropsychological profile of children and adolescents with this disorder. The influence of clinical variables such as age, severity of obsessive-compulsive symptomatology, depressive symptomatology, and pharmacological treatment on cognitive performance in these patients has not been thoroughly studied. METHODS A neuropsychological battery designed for this study was administered to 35 patients with DSM-IV-TR diagnosis of OCD without psychiatric comorbidity aged between 7 and 18 years and 35 gender- and age-matched healthy subjects. RESULTS Children and adolescents with OCD performed significantly worse on verbal and visual memory and velocity. When depressive symptomatology was controlled, impairment in visual memory, visual organization, and velocity again was found, but impairment in verbal memory was not. Neuropsychological impairment was not related to age, obsessive-compulsive severity, and pharmacological treatment. CONCLUSIONS Children and adolescents with OCD without psychiatric comorbidity with acute illness show impairment in visual memory, visual organization, and velocity, similar to adults. The influence of depressive symptomatology is important in cognitive performance. No relation was found between neuropsychology and age, severity of obsessive-compulsive symptomatology, or pharmacological treatment in this study.

Cerebral activation in children and adolescents with obsessive–compulsive disorder before and after treatment: A functional MRI study

BACKGROUND Structural and functional fronto-striatal abnormalities are involved in the pathophysiology of obsessive-compulsive disorder (OCD). The aims of the present study were: (a) to investigate possible regional brain dysfunction in premotor cortico-striatal activity in drug-naïve children and adolescents with OCD; (b) to correlate brain activation with severity of obsessive-compulsive symptomatology; and (c) to detect possible changes in brain activity after pharmacological treatment. METHOD Twelve children and adolescents (age range 7-18 years; seven male, five female) with DSM-IV obsessive-compulsive disorder and twelve healthy subjects matched for age, sex and intellectual level were studied. Functional magnetic resonance imaging data were obtained during the performance of simple and complex sequences. RESULTS Comparing the complex motor condition with the simple control condition, both patients and controls showed a pattern of cerebral activation involving the fronto-parietal cortex and basal ganglia. Compared with controls, OCD patients presented significantly higher brain activation bilaterally in the middle frontal gyrus. After 6 months of pharmacological treatment and with clear clinical improvement, activation in the left insula and left putamen decreased significantly. CONCLUSION In a paediatric OCD sample that was treatment naïve and without another psychiatric disorder we showed hyperactivation of the circuits that mediate symptomatic expression of OCD. The cerebral activation decreases after treatment and clinical improvement.

Adolescent Anorexia Nervosa: The Catch-up Effect in Bone Mineral Density After Recovery

OBJECTIVE To determine whether bone mineral density (BMD) loss can be reversed in adolescent anorexic patients. METHOD A prospective study with 108 anorexia nervosa patients (DSM-IV) from 12 to 17 years of age at the Eating Disorders Unit in the Hospital Clinic of Barcelona (Spain). They were first evaluated by dual-energy x-ray absorptiometry in lumbar spine and femoral neck consecutively from 1997 until 1999 and reexamined after 6 to 30 months. Results were compared with normative values of bone mass. RESULTS Patients with poor outcome (n = 44) had a bone mass loss. Patients with good short-term outcome were divided in two groups. The group with normal BMD at first evaluation (n = 41) had a bone mass gain per year of 3.0% at lumbar spine and 0.5% at femoral neck. The group with low BMD at first evaluation (n = 23) had an increase per year of 9.1% at lumbar spine and 4.5% at femoral neck. In a multiple linear regression analysis with the variables body mass index, age, months with menstruation, and BMD zscore at first evaluation, the only predictor of BMD increase was the first z score both at the lumbar spine (coefficient R = 0.64; p < .001) and at the femoral neck (coefficient R = 0.5; p < .001). CONCLUSIONS There is a catch-up effect in adolescent patients with low BMD but good short-term outcome.

A cross-sectional and follow-up functional MRI study with a working memory task in adolescent anorexia nervosa

Structural and functional brain abnormalities have been described in anorexia nervosa (AN). The objective of this study was to examine whether there is abnormal regional brain activation during a working memory task not associated with any emotional stimuli in adolescent patients with anorexia and to detect possible changes after weight recovery. Fourteen children and adolescents (age range 11-18 years) consecutively admitted with DSM-IV diagnosis of AN and fourteen control subjects of similar age were assessed by means of psychopathological scales and functional magnetic resonance imaging (fMRI) during a working memory task. After seven months of treatment and weight recovery, nine AN patients were reassessed. Before treatment, the AN group showed significantly higher activation than controls in temporal and parietal areas and especially in the temporal superior gyrus during performance of the cognitive task. Control subjects did not show greater activation than AN patients in any region. A negative correlation was found between brain activation and body mass index and a positive correlation between activation and depressive symptomatology. At follow-up after weight recovery, AN patients showed a decrease in brain activation in these areas and did not present differences with respect to controls. These results show that adolescent AN patients showed hyperactivation in the parietal and especially the temporal lobe during a working memory task, suggesting that they must make an additional effort to perform at normal levels. This activation correlated with clinical variables. In these young patients, differences with respect to controls disappeared after weight recovery.

Intrinsic connectivity networks from childhood to late adolescence: Effects of age and sex

Highlights • We assessed intrinsic connectivity of networks underlying cognition in youth.• Evidence of age effects on intrinsic connectivity was found across all networks.• Intrinsic connectivity showed no effect of sex, nor age by sex interactions.

D8/17 monoclonal antibody: an unclear neuropsychiatric marker.

Objective: It has been hypothesized that monoclonal antibody D8/17 identifies a B lymphocyte antigen with expanded expression in patients with rheumatic fever, childhood onset obsessive-compulsive disorder (OCD), Tourette syndrome (TS) or prepubertal anorexia nervosa (AN). Our purpose was to replicate these studies in a Spanish population and to determine whether D8/17 identifies a subgroup of these patients, focusing especially on OCD subjects. Method: D8/17 expression was assessed with double immunofluorescence and flow cytometry using monoclonal immunoglobulin M (IgM) in three groups of patients with diagnoses of OCD (n = 17), TS (n = 5) and prepubertal AN (n = 5), recruited during 2001. Results: In the sample studied the average percentage of B cells expressing D8/17 was 4.8%. The D8/17 positive proportion of B lymphocytes was above 11% in only two out of 17 OCD patients (7.4% of total sample) and in none of the TS or prepubertal AN patients. No statistically significant differences were found in mean percentages of D8/17 between the three groups. Conclusions: In the sample studied the expression of D8/17 in B cells was very low and the great majority of patients were negative for the D8/17 marker. The molecular characterization of D8/17 would be a major step forward in clarifying its implication for these diseases.

Normal gray and white matter volume after weight restoration in adolescents with anorexia nervosa

OBJECTIVE The aim of this study was to determine whether treated, weight-stabilized adolescents with anorexia nervosa (AN) present brain volume differences in comparison with healthy controls. METHOD Thirty-five adolescents with weight-recovered AN and 17 healthy controls were assessed by means of psychopathology scales and magnetic resonance imaging. Axial three-dimensional T1-weighted images were obtained in a 1.5 Tesla scanner and analyzed using optimized voxel-based morphometry (VBM). RESULTS There were no significant differences between controls and weight-stabilized AN patients with regard to global volumes of either gray or white brain matter, or in the regional VBM study. Differences were not significant between patients with psychopharmacological treatment and without, between those with amenorrhea and without, as well as between patients with restrictive versus purgative AN. DISCUSSION The present findings reveal no global or regional gray or white matter abnormalities in this sample of adolescents following weight restoration.

A voxel-based morphometric MRI study of stabilized obsessive–compulsive adolescent patients

BACKGROUND The aim of this study was to determine whether treated stabilized adolescents with obsessive-compulsive disorder (OCD) present brain structure differences in comparison with healthy control subjects. METHODS Twenty-seven adolescents with already-treated OCD and 27 healthy controls matched by age, sex and estimated intellectual level were assessed by means of psychopathological scales and magnetic resonance imaging (MRI). Axial three-dimensional T1-weighted images were obtained in a 1.5 T scanner and analyzed using optimized voxel-based morphometry (VBM). RESULTS Compared with controls, stabilized patients with OCD did not present any statistical differences in the whole brain. However, a small volume correction analysis yielded significant results that survived correction for multiple comparisons, showing decreased white matter (WM) volume in a small area of the parietal cortex (t=3.39, p=0.045 FWE (family wise error)-corrected) of OCD patients in comparison with healthy controls. There was no significant correlation between decreased WM volume in the parietal cortex and obsessive-compulsive symptomatology. CONCLUSION There were no global significant differences in either gray matter (GM) or WM. Small differences were found between adolescent patients with stabilized OCD and healthy controls as regards in WM volume in right parietal areas. The parietal lobe may play a role in the pathophysiology of OCD, even in clinically stabilized patients.