Blood Parameters in Children and Adolescents With Underweight and Atypical Anorexia Nervosa.

OBJECTIVE: This study aimed to identify biochemical, hematological, and endocrinological abnormalities in a sample of children and adolescents with underweight AN and atypical AN and to compare these results between the two groups. METHOD: Based on the 5th BMI-percentile admission, adolescents with underweight AN (n = 520) and atypical AN (n = 255) were included and medical records were reviewed. RESULTS: Low prealbumin (35%) and neutropenia (39%), and several abnormalities in endocrinological parameters (50%) were the most common alterations found in the whole sample. Compared to the atypical AN group, the underweight AN group had significantly higher frequencies of elevated cholesterol (OR = 2.50; p < 0.001) and alanine aminotransferase (OR = 0.22; p = 0.005) and of reduced insulin-like growth (IGF) factor-1 (OR = 0.29; p < 0.001), T3 (OR = 0.46; p < 0.001), luteinizing hormone (OR = 0.24; p < 0.001), follicle stimulating hormone (OR = 0.58; p = 0.004), and 17b-estradiol (OR = 0.39; p < 0.001). However, other blood parameters showed similar alterations in both groups. DISCUSSION: Both groups showed abnormalities in the same blood parameters, but some abnormal parameters were more common in the underweight AN group. These results suggest that atypical AN and underweight AN could present similar risks of certain medical complications.

Clinical significance of psychiatric comorbidity in children and adolescents with obsessive-compulsive disorder: subtyping a complex disorder.

A promising approach in relation to reducing phenotypic heterogeneity involves the identification of homogeneous subtypes of OCD based on age of onset, gender, clinical course and comorbidity. This study aims to assess the sociodemographic characteristics and clinical features of OCD patients in relation to gender and the presence or absence of another comorbid disorder. The sample comprised 112 children and adolescents of both sexes and aged 8-18 years, all of whom had a diagnosis of OCD. Overall, 67 % of OCD patients had one comorbid diagnosis, 20.5 % had two such diagnoses and 2.6 % had three comorbid diagnoses. The group of OCD patients with a comorbid neurodevelopmental disorder had significantly more family history of OCD in parents (p = .049), as compared with the no comorbidity group and the group with a comorbid internalizing disorder, and they also showed a greater predominance of males (p = .013) than did the group with a comorbid internalizing disorder. The group of OCD patients with internalizing comorbidity had a later age of onset of OCD (p = .001) compared with both the other groups. Although the initial severity was similar in all three groups, the need for pharmacological treatment and for hospitalization due to OCD symptomatology was greater in the groups with a comorbid neurodevelopmental disorder (p = .038 and p = .009, respectively) and a comorbid internalizing disorder (p = .008 and p = .004, respectively) than in the group without comorbidity. Our findings suggest that two subtypes of OCD can be defined on the basis of the comorbid pathology presented. The identification of different subtypes according to comorbidity is potentially useful in terms of understanding clinical variations, as well as in relation to treatment management and the use of therapeutic resources.

One-Year Follow-up of Children and Adolescents with Major Depressive Disorder: Relationship between Clinical Variables and Abcb1 Gene Polymorphisms.

Introduction: Differences in response to fluoxetine (FLX) may be influenced by certain genes that are involved in FLX transportation (ABCB1). We examined remission and recovery from the index episode in a cohort of patients treated with FLX, and also investigated associations between genetic variants in ABCB1 and remission, recovery, and suicide risk. Methods: This was a naturalistic 1-year follow-up study of 46 adolescents diagnosed with major depressive disorder (MDD). At 12 months they underwent a diagnostic interview with the K-SADS-PL. Results: It was found that remission was around 69.5% and recovery 56.5%. Remission and recovery were associated with lower scores on the CDI at baseline, with fewer readmissions and suicide attempts, and with lower scores on the CGI and higher scores on the GAF scale. No relationship was found between ABCB1 and remission or recovery. However, a significant association was observed between the G2677T ABCB1 polymorphism and suicide attempts. Conclusion: Other factors such as stressful events, family support, and other genetic factors are likely to be involved in MDD outcome.

Effect of CYP2D6, CYP2C9 and ABCB1 genotypes on fluoxetine plasma concentrations and clinical improvement in children and adolescent patients.

There is little known about pharmacogenetic of fluoxetine in children and adolescents. In this study, we evaluate, for the first time, the influence of CYP2D6, CYP2C9 and ABCB1 genotypes on the steady-state plasma concentrations of fluoxetine and its active metabolite (S)-norfluoxetine, and on the clinical improvement in children and adolescent patients receiving fluoxetine treatment. The assessment was performed in 83 patients after 8 and 12 weeks of treatment. Fluoxetine/(S)-norfluoxetine ratio was negatively correlated with the number of active CYP2D6 alleles (r: -0.450; P<0.001). Regarding the G2677T ABCB1 polymorphism, T allele carriers showed significantly higher improvements on the majority of scales including the Clinical Global Impression-Improvement scale (P<0.001). Our results confirm the influence of CYP2D6 genetic variants in fluoxetine pharmacokinetics and provide evidence for the potential effect of the ABCB1 genotype on the clinical improvement in children and adolescent patients treated with fluoxetine.

Long-term cardiac assessment in a sample of adolescent-onset anorexia nervosa.

BACKGROUND: High mortality rates have been reported in patients with anorexia nervosa, mainly due to cardiovascular alterations. The purpose of the present study was to assess cardiac structural and functional abnormalities some 20 years after initial treatment in a sample of adolescent-onset anorexia nervosa (A-AN) and to compare them with matched healthy controls (HC). METHODS: A sample of 29 women diagnosed and treated for AN during adolescence (A-AN) were assessed more than 20 years later. A complete cardiac evaluation was carried out including an electrocardiogram (ECG) and a standard 2D echocardiography. Thirty matched HC were also assessed. RESULTS: In the A-AN group, four subjects had a body mass index lower than 18.5 and met full DSM 5 criteria for AN at follow-up (Low-Weight group). They were compared with the rest of the sample (n = 25) who had normalized their weight (Normal-Weight group), though some still showed some eating disorder symptoms. Both groups were compared with the HC group. Subjects in the Low-Weight group presented statistically significant decreases in the left ventricular end-diastolic and left atrium dimensions and left ventricular mass in comparison with the Normal-Weight group and the HC. No other differences in cardiac parameters were found between groups. CONCLUSIONS: Echocardiographic and ECG parameters of adults who had presented A-AN twenty years earlier and currently maintained normal weight were similar to those of HC who had never been treated or diagnosed with AN. Adult subjects with A-AN who still had low weight in the long term present certain cardiac abnormalities similar to those seen in short-lasting disease. More studies are needed to confirm these results in a larger sample.

Anorexia nervosa is associated with multiple medical complications and high mortality, mainly due to cardiovascular complications. The main objective of the project was to study long-term cardiac abnormalities in a group of patients diagnosed with anorexia nervosa during adolescence. A sample of 29 patients, treated during adolescence for anorexia nervosa, were evaluated 20 years later. We did an echocardiogram and an electrocardiogram to all of them, and compared them with 30 healthy controls. Of the 29 patients with anorexia nervosa, 4 had low weight and 25 had normal weight. Patients who had normalized their weight did not present cardiac alterations and did not differ from the healthy controls. The 4 underweight patients did present cardiac abnormalities similar to those observed in short-term studies, such as decreased dimensions and mass of the left ventricle and the left atrium.

1H-MRS of the anterior cingulate cortex in childhood and adolescent obsessive-compulsive disorder: a case-control study.

Abnormal glutamate concentrations in the anterior cingulate cortex (ACC) have been identified in children and adults with obsessive-compulsive disorder (OCD). The purpose of the present study was to measure in vivo (1)H-MRS neurometabolite concentrations in the ACC of children and adolescents with OCD, in order to identify metabolite abnormalities compared to healthy controls and to assess their relationship with clinical variables. 3T proton-magnetic resonance spectroscopy was used to probe ACC biochemistry in 47 paediatric and adolescent OCD patients (11-18 years old) compared to 31 healthy subjects of similar age, sex and estimated intellectual quotient. There were no significant differences in the concentration of glutamate plus glutamine (Glx) adjusted for CSF between OCD patients and healthy controls [F1,74=0.00; P=0.943], but there were significant differences in the concentration of Glx adjusted for CSF in paediatric and adolescent OCD patients according to duration of illness (less than or more than 24 months) [F2,73=3.95; P=0.024]. In addition, we found significantly lower levels of myo-inositol adjusted for CSF in the ACC [F1,74=5.686; P=0.02] in patients compared with controls. The present findings do not confirm the hypothesis of differences in Glx concentrations in the ACC between children and adolescents with OCD and healthy controls; however, the observation of differences in the Glx concentration in children and adolescent OCD patients depending on the duration of illness is of interest.

Role of GAD2 and HTR1B genes in early-onset obsessive-compulsive disorder: results from transmission disequilibrium study.

One of the leading biological models of obsessive-compulsive disorder (OCD) is the frontal-striatal-thalamic model. This study undertakes an extensive exploration of the variability in genes related to the regulation of the frontal-striatal-thalamic system in a sample of early-onset OCD trios. To this end, we genotyped 266 single nucleotide polymorphisms (SNPs) in 35 genes in 84 OCD probands and their parents. Finally, 75 complete trios were included in the analysis. Twenty SNPs were overtransmitted from parents to early-onset OCD probands and presented nominal pointwise P < 0.05 values. Three of these polymorphisms achieved P < 2 × 10(-4), the significant P-value after Bonferroni corrections: rs8190748 and rs992990 localized in GAD2 and rs2000292 in HTR1B. When we stratified our sample according to gender, different trends were observed between males and females. In males, SNP rs2000292 (HTR1B) showed the lowest P-value (P = 0.0006), whereas the SNPs in GAD2 were only marginally significant (P = 0.01). In contrast, in females HTR1B polymorphisms were not significant, whereas rs8190748 (GAD2) showed the lowest P-value (P = 0.0006). These results are in agreement with several lines of evidence that indicate a role for the serotonin and γ-Aminobutyric acid (GABA) pathways in the risk of early-onset OCD and with the gender differences in OCD pathophysiology reported elsewhere. However, our results need to be replicated in studies with larger cohorts in order to confirm these associations.