Accuracy of estimating self and other body size among adolescent girls with anorexia nervosa.

This study aimed to analyze body size estimates of others by patients with anorexia nervosa (AN) and to identify any differences with the perception of their own body size. Adolescent females (age, 13-17 years) were enrolled into AN (n = 30) and control(n = 23) groups. The Subjective Body Dimensions Apparatus (SBDA) was used to evaluate body size estimates for oneself (self-estimation) and others (other-estimation). Participants also completed questionnaires assessing eating disorders and depressive symptoms. The AN and control groups scored significantly higher in self-estimation than in other-estimation. However, the AN group showed higher self-estimation scores than the control group for all the body parts and for the global silhouette (p < .001). Patients with more severe eating disorder symptomatology showed more distorted self-estimation (p < .05). No statistically significant differences were found in the other-estimation scores between the groups (p = .714), indicating that AN and control patients estimate the body sizes of others similarly. Eating disorder symptomatology correlates with self-estimation scores but not with other-estimation scores in adolescents with AN. No correlations existed between clinical symptomatology and other-estimation.

Longitudinal study in adolescent anorexia nervosa: evaluation of cortico-striatal and default mode network resting-state brain circuits.

Anorexia nervosa (AN) typically emerges in adolescence. The cortico-striatal system (CSTS) and the default mode network (DMN) are brain circuits with a crucial development during this period. These circuits underlie cognitive functions that are impaired in AN, such as cognitive flexibility and inhibition, among others. Little is known about their involvement in adolescent AN and how weight and symptom improvement might modulate potential alterations in these circuits. Forty-seven adolescent females (30 AN, 17 healthy control) were clinically/neuropsychologically evaluated and scanned during a 3T-MRI resting-state session on two occasions, before and after a 6-month multidisciplinary treatment of the AN patients. Baseline and baseline-to-follow-up between-group differences in CSTS and DMN resting-state connectivity were evaluated, as well as their association with clinical/neuropsychological variables. Increased connectivity between the left dorsal putamen and the left precuneus was found in AN at baseline. At follow-up, body mass index and clinical symptoms had improved in the AN group. An interaction effect was found in the connectivity between the right dorsal caudate to right mid-anterior insular cortex, with lower baseline AN connectivity that improved at follow-up; this improvement was weakly associated with changes in neuropsychological (Stroop test) performance. These results support the presence of CSTS connectivity alterations in adolescents with AN, which improve with weight and symptom improvement. In addition, at the level of caudate-insula connectivity, they might be associated with inhibitory processing performance. Alterations in CSTS pathways might be involved in AN from the early stages of the disorder.

Functional impairment in a Spanish Sample of Children and Adolescents with Obsessive-Compulsive Disorder.

The Child Obsessive-Compulsive Impact Scale (COIS-R) is a parent- and self-report measure of the impairment related to Obsessive-Compulsive Disorder (OCD) symptoms. Previous research has demonstrated the reliability and validity of the original version of the COIS-R; to date, however, the scale has not been validated for use in Spanish samples of pediatric OCD. The present study aimed to assess the psychometric properties of this in a clinical sample of pediatric OCD (n = 91). Analyses of internal consistency, convergent and divergent validity were conducted. For both the COIS-R report scales estimates similar to those in the original instrument were obtained for internal consistency, test-retest reliability, and convergent validity. Thus, the Spanish version of the COIS-R seems to retain sound psychometric properties of its original version; it appears to be a reliable instrument for the assessment of obsessive-compulsive impairment and the effects of treatment, and can be used in other cultural contexts.

Cortical thickness 20 years after diagnosis of anorexia nervosa during adolescence.

OBJECTIVE: The objective of the present study is to evaluate cortical thickness (CT) abnormalities using FreeSurfer in adult subjects who had an onset of anorexia nervosa during their adolescence some 20 years previously, and to compare them with control subjects. METHODS: Fifty-four participants, including 26 women who were diagnosed and treated for AN during adolescence some 20 years previously and 28 healthy women of similar age and geographical area were assessed using structured interviews and MRI scans. Prior AN subjects were divided into two groups depending on their current eating disorder status (recovered or not recovered from any eating disorder). In all subjects, CT was measured using FreeSurfer. RESULTS: A significantly lower CT was observed in the eating disorder group than in the control group in the right post-central gyrus and the lateral occipital cortex. The recovered eating disorder group only had lower CT in the post-central gyrus. Within all subjects with prior AN, no correlations were found between lower CT in these areas and clinical variables. DISCUSSION: CT is reduced some 20 years after diagnosis of AN especially in the parietal and precentral areas, even in subjects without any current ED diagnosis.

Personality disorder traits, obsessive ideation and perfectionism 20 years after adolescent-onset anorexia nervosa: a recovered study.

PURPOSE: The many studies examining the relationship between anorexia nervosa (AN) and personality abnormalities have observed high comorbidity. However, no definitive studies to date have established whether there is a causal connection or whether it is a complication. The current study aimed to explore the nature of the relationship between personality disorder (PD) traits, obsessionality and perfectionism, using a study design that allows the testing of some comorbidity models. METHODS: Twenty-nine women were recruited from a group of former AN patients treated during their adolescence in a specialized unit around 20 years before the time of this study. They were divided into two groups according to the current presence of eating disorder (ED) symptoms (current-ED, n = 11; recovered, n = 18). Both groups were compared to a matched control group (n = 29) regarding current PD traits, obsessive beliefs and perfectionism. RESULTS: Borderline PD traits, most cluster C PD traits and overestimation of threat were more common in the current-ED group than in the control and recovered groups. Obsessive-compulsive PD traits, intolerance of uncertainty, and perfectionism were also significantly more prevalent in the current-ED group compared to controls but did not reach significance when compared to the recovered group. No significant differences were found between the recovered and control groups. CONCLUSION: Our results mostly support the personality abnormalities observed as a transient effect related to the presence of ED psychopathology in patients with adolescent-onset AN. LEVEL OF EVIDENCE: Level III, case-control analytic studies.

Validation of the Caregiver Skills (CASK) scale in Catalonia: Concordance between caregivers in attitudes and behaviours.

OBJECTIVE: The aim of this study was to validate a Spanish version of the Caregiver Skills scale (CASK) in a sample of eating disorder (ED) caregivers. A further aim was to examine the concordance/discrepancy between them (namely, between the mothers and fathers of ED patients). METHOD: Two hundred sixty-five ED caregivers were recruited from ED centers in Catalonia, Spain. Confirmatory factor analyses was used to test the factorial structure of the CASK scale. Cronbach's α was used to measure internal consistency of the CASK scales. A comparison of the CASK measures between respondents (mothers and fathers) was conducted using generalized estimating equations. RESULTS: Confirmatory factor analysis of the Spanish version of the CASK corroborated the strong factorial validity of the 6 factors of the original CASK questionnaire. Mothers and fathers did not differ significantly on CASK overall and subscale scores. There was however less concordance between parents on the bigger picture (ICC = 0.28) and biting your tongue (ICC = 0.08) subscales. CONCLUSIONS: The CASK is a valid tool to assess ED-related attitudes in Spanish-speaking caregivers. Furthermore, caregivers and patients alike could stand to benefit from interventions focused on improving areas such as ED beliefs, effective communication, quality of life, and emotional distancing.

Plasma fluoxetine concentrations and clinical improvement in an adolescent sample diagnosed with major depressive disorder, obsessive-compulsive disorder, or generalized anxiety disorder.

UNLABELLED: Fluoxetine (FLX) has been one of the most widely studied selective serotonin reuptake inhibitors in adolescents. Despite its efficacy, however, 30% to 40% of patients do not respond to treatment. AIMS: The aim of this study was to evaluate whether clinical improvement or adverse events are related to the corrected dose of FLX at 8 and 12 weeks after starting treatment in a sample of adolescents diagnosed with major depressive disorder, obsessive-compulsive disorder, or generalized anxiety disorder. METHODS: Seventy-four subjects aged between 10 and 17 years participated in the study. Clinical improvement was measured with the Clinical Global Impression-Improvement Scale, whereas the UKU (Udvalg for Klinske Undersogelser) scale was administered to assess adverse effects of treatment. RESULTS: Fluoxetine per kilograms of body weight was related to serum concentration of FLX, NORFLX (norfluoxetine), FLX + NORFLX, and FLX/NORFLX. No relationship was found between dose-corrected FLX levels and therapeutic or adverse effects. No differences in serum concentrations were found between responders and nonresponders to treatment. Sex differences were observed in relation to dose and FLX serum concentration. The analysis by diagnosis revealed differences in FLX dose between obsessive-compulsive disorder patients and both generalized anxiety disorder and major depressive disorder patients. CONCLUSIONS: Fluoxetine response seems to be influenced by factors such as sex, diagnosis, or certain genes that might be involved in the drug's pharmacokinetics and pharmacodynamics. Clinical and pharmacogenetic studies are needed to elucidate further the differences between treatment responders and nonresponders.

Delusional beliefs in adolescents with anorexia nervosa, obsessive-compulsive disorder, or first-episode psychosis: A comparative study.

Delusional thinking is a key symptom of first-episode psychosis (FEP), but it has also been studied in obsessive-compulsive disorder (OCD) and anorexia nervosa (AN). This study aimed to analyze the psychometric properties of the Brown Assessment of Beliefs Scale (BABS) in a sample of adolescents diagnosed with a FEP, AN, or OCD, and to compare delusional thinking among the three samples. The sample comprised 60 patients in three groups of 20 diagnosed with OCD, AN, or FEP. Participants underwent assessment by diagnostic interview, the BABS scale, and a measure of depressive symptomatology. Specific instruments were also used to assess the main symptomatology of each disorder. The BABS had good internal consistency, and high validity and reliability. The OCD group scored significantly lower than the other two groups in all scale items except for items 4 (fixation of ideas), 6 (insight), and 7 (delusions of reference). A significant difference only existed between the AN and FEP groups for item 7 (delusions of reference). The BABS scale is a valid and reliable tool for assessing delusionality in adolescents diagnosed with OCD, AN, or FEP, with evidence of marked differences between the disorders. Assessing these symptoms could influence management, helping to improve treatment adherence and prognosis.

Increase in admission rates and symptom severity of childhood and adolescent anorexia nervosa in Europe during the COVID-19 pandemic: data from specialized eating disorder units in different European countries.

BACKGROUND: The COVID-19 pandemic, associated with confinement and social isolation, seems to have impacted the course of many mental disorders in children and adolescents. An increase in hospital admission rates for juvenile anorexia nervosa (AN) has been documented in many regions of the world. However, data from Europe are scarce. METHODS: We asked clinicians in specialized eating disorder units in hospitals of maximum care in France, Germany, Italy, Spain, Sweden, and the Netherlands to report on (i) overall (inpatient and outpatient) and (ii) inpatient admission rates for adolescents with AN during 2019 and 2020. Additionally, a modified version of the COVID Isolation Eating Scale (CIES) was used to assess the child and adolescent psychiatrists' estimations of a possible increase in symptom severity in children and adolescents with AN during the COVID-19 pandemic and to (iii) inquire about the contributing factors perceived by the caring professionals. RESULTS: Four out of six representatives of European hospitals described a higher rate of overall admissions during the pandemic. Three hospitals out of six reported an increase in inpatient admissions, and two centres had constant high numbers of admissions of both outpatients and inpatients. The clinicians perceived a higher symptom severity in 2020 than in 2019, especially involving more frequent use of social media, longer duration of exercising, and more restrictive eating. They supposed an increase in social media consumption, a perceived "loss of control", and a lack of in-person assessments and weight controls as the main contributing factors for the deterioration in AN numbers and symptomatology. CONCLUSIONS: The COVID-19 pandemic seems to have had a deep impact on symptom severity in AN, which is mirrored by a large increase in admission rates across Europe. An increase in exercise, social media consumption, a perceived "loss of control", and a lack of face-to-face health care seem to have contributed to this development. Further investigation is required to identify which factors may lead to the increase in incidence and deterioration of childhood and adolescent AN. Possible preventive means for the future could include educating paediatricians and health care workers about AN, regular weight assessment, and home-based treatments.

DNA Methylation of Fluoxetine Response in Child and Adolescence: Preliminary Results.

PURPOSE: The search for predictors of antidepressant response is gaining increasing attention, with epigenetic markers attracting a great deal of interest. We performed a genome-wide study assessing baseline differences in DNA methylation between Responders and Non-Responders. PATIENTS AND METHODS: Twenty-two children and adolescents, receiving fluoxetine treatment for the first time, were classified as Responders or Non-Responders according to CGI-I score after 8 weeks of fluoxetine treatment. Genome-wide DNA methylation was profiled using the Illumina Infinium MethylationEPIC BeadChip Kit and analyzed using the Chip Analysis Methylation Pipeline (ChAMP). RESULTS: We identified 21 CpG sites significantly (FDR<0.05) associated with fluoxetine response that showed meaningful differences (Δß> ±0.2) in methylation level between Responders and Non-Responders. Two genes, RHOJ (Ras Homolog Family Member J) and OR2L13 (Olfactory Receptor family 2 subfamily L member 13), presented more than one significant CpG sites. CONCLUSION: Our findings provide new insights into the molecular mechanisms underlying the complex phenotype of antidepressant response, indicating that methylation at specific genes could be a promising biomarker that needs further replication in large cohorts.

Long-term outcome and psychiatric comorbidity of adolescent-onset anorexia nervosa.

OBJECTIVE: To assess the outcome of adolescents with anorexia nervosa (AN) about 20 years after first treatment. METHODS: Sixty-two women diagnosed with AN during adolescence were invited to participate. Of these 62 patients, 38 agreed to participate and were assessed with a battery of questionnaires and interviews. A control group of 30 women of similar age was also assessed. RESULTS: Of the patients who completed the full assessment, 13 (34%) presented some degree of eating disorder (ED) at follow-up (10 (26%) met full Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) criteria for an ED and 3 (8%) showed partial remission of an ED). The remaining 25 (66%) patients had fully recovered from AN. The duration of untreated illness before admission was significantly associated with an increased risk of a current ED (odds ratio (OR) = 3.334 (1.3-8.7); p = .014). Of the patients who had recovered totally from their ED, 24% showed another psychiatric disorder. This percentage rose to 70% in patients with a current ED. CONCLUSION: Sixty-six percent of adolescents who completed the assessment achieved remission of their AN. Comorbidity was more common in the current ED group. The variable that best predicted complete remission was the number of years without treatment, showing the importance of detection and early intervention.

Response to fluoxetine in children and adolescents: a weighted gene co-expression network analysis of peripheral blood.

The inconclusive and non-replicated results of pharmacogenetic studies of antidepressant response could be related to the lack of acknowledgement of its mechanism of action. In this scenario, gene expression studies provide and interesting framework to reveal new candidate genes for pharmacogenetic studies or peripheral biomarkers of fluoxetine response. We propose a system biology approach to analyse changes in gene expression induced by eight weeks of treatment with fluoxetine in peripheral blood. 21 naïve child and adolescents participated in the present study. Our analysis include the identification of gene co-expression modules, using Weighted Gene Co-expression Network Analysis (WGCNA), followed by protein-protein interaction (PPi) network construction coupled with functional annotation. Our results revealed two modules of co-expression genes related to fluoxetine treatment. The constructed networks from these modules were enriched for biological processes related to cellular and metabolic processes, cell communication, immune system processes, cell death, response to stimulus and neurogenesis. Some of these processes, such as immune system, replicated previous findings in the literature, whereas, neurogenesis, a mechanism proposed to be involved in fluoxetine response, had been identified for first time using peripheral tissues. In conclusion, our study identifies several biological processes in relation to fluoxetine treatment in peripheral blood, offer new candidate genes for pharmacogenetic studies and valuable markers for peripheral moderator biomarkers discovery.

A cross-sectional and follow-up voxel-based morphometric MRI study in adolescent anorexia nervosa.

The objective was to examine whether cerebral volumes are reduced, and in what regions, in adolescents with anorexia nervosa and to study changes after nutritional recovery. Twelve anorexia nervosa (DSM-IV) patients aged 11-17 consecutively admitted to an Eating Disorders Unit were assessed by means of psychopathological scales, neuropsychological battery and voxel-based morphometric (VBM) magnetic resonance imaging at admission and after 7 months' follow-up. Nine control subjects of similar age, gender and estimated intelligence level were also studied. The two groups showed differences in gray matter (F=22.2; p<0.001) and cerebrospinal fluid (CSF) (F=21.2; p<0.001) but not in white matter volumes. In anorexic patients, gray matter volume correlated negatively with the copy time from the Rey Complex Figure Test. In the regional VBM study several temporal and parietal gray matter regions were reduced. During follow-up there was a greater global increase in gray matter (F=10.7; p=0.004) and decrease in CSF (F=22.1; p=0.001) in anorexic patients. The increase in gray matter correlated with a decrease in cortisol (Spearman correlation=-0.73; p=0.017). At follow-up there were no differences in global gray matter (F=2.1; p=0.165), white matter (F=0.02, p=0.965) or CSF (F=1.8; p=0.113) volumes between both groups. There were still some smaller areas, in the right temporal and both supplementary motor area, showing differences between them in the regional VBM study. In conclusion, in adolescent anorexic patients gray matter is more affected than white matter and mainly involves the posterior regions of the brain. Overall gray matter alterations are reversible after nutritional recovery.

Comparison of Perfectionism Dimensions in Adolescents with Anorexia Nervosa or Obsessive-Compulsive Disorder.

OBJECTIVE: The aim of the study was to compare two dimensions of perfectionism, namely self-oriented perfectionism (SOP) and socially prescribed perfectionism (SPP), in adolescents with anorexia nervosa (AN) or obsessive-compulsive disorder (OCD) and in healthy controls. A further objective was to investigate the influence of perfectionism dimensions on obsessive-compulsive, depressive, and eating symptomatology. METHODS: A total of 79 adolescents with AN, 32 with OCD, and 74 healthy controls were recruited. The Child and Adolescent Perfectionism Scale (CAPS) was used to assess SOP and SPP. Measures of depression, obsessive-compulsive and eating symptomatology were administered. RESULTS: The AN group scored higher on SOP than did both the OCD group (p < 0.001) and controls (p < 0.001). In the AN group, SOP accounted for significant variance in scores on the obsessive (p < 0.001), depressive (p < 0.001), and eating symptomatology (p = 0.001), and the interaction between group and SOP was statistically significant when compared with the controls. Mean SPP total score among controls was similar to that in the AN group and higher than that in the OCD group (p = 0.003). Only in the control group did SPP account for significant variance in scores on the measures of obsessive-compulsive (p = 0.002), depression (p = 0.011), and eating symptomatology (p = 0.006). CONCLUSIONS: Self-oriented perfectionism seemed more specific to AN than to OCD or controls. It predicted obsessive-compulsive, depressive, and eating symptoms in the AN group. In healthy controls, SPP was related to obsessive-compulsive, depressive, and eating symptomatology.

OBJECTIF: Le but de l'étude était de comparer les deux dimensions du perfectionnisme, notamment le perfectionnisme auto-orienté (PAO) et le perfectionnisme imposé socialement (PIS), chez des adolescents souffrant d'anorexie mentale (AM) ou du trouble obsessionnel-compulsif (TOC) et chez des sujets témoins. Un autre objectif était d'investiguer l'influence des dimensions du perfectionnisme sur le trouble obsessionnel-compulsif, le trouble dépressif et la symptomatologie alimentaire. MÉTHODES: Ont été recrutés 79 adolescents souffrant d'AM, 32 souffrant du TOC et 74 sujets témoins. L'échelle du perfectionnisme pour enfants et adolescents (CAPS) a servi à évaluer le PAO et le PIS. Des mesures de la dépression, du trouble obsessionnel-compulsif et de la symptomatologie alimentaire ont été administrées. RÉSULTATS: Le groupe d'AM a eu des scores plus élevés au PAO que le groupe du TOC (p < 0,001) et le groupe des témoins (p < 0,001). Dans le groupe d'AM, le PAO représentait une variance significative des scores aux troubles obsessionnels (p < 0,001), dépressifs (p < 0,001), et à la symptomatologie alimentaire (p = 0,001), et l'interaction entre le groupe et le PAO était statistiquement significative lorsque comparée avec les témoins. Le score total moyen du PIS chez les témoins était semblable à celui du groupe d'AM et plus élevé que celui du groupe du TOC (p = 0,003). C'est seulement dans le groupe témoins que le PIS représentait une variance significative des scores aux mesures du trouble obsessionnel-compulsif (p = 0,002), de la dépression (p = 0,011), et de la symptomatologie alimentaire (p = 0,006). CONCLUSIONS: Le perfectionnisme auto-orienté semblait plus spécifique à l'AM qu'au TOC ou aux témoins. Il prédisait les symptômes obsessionnels-compulsifs, dépressifs et alimentaires dans le groupe d'AM. Chez les témoins en santé, le PIS était lié aux symptômes obsessionnels-compulsifs, dépressifs et alimentaires.

Genetic Associations of Serotoninergic and GABAergic Genes in an Extended Collection of Early-Onset Obsessive-Compulsive Disorder Trios.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder whose etiology includes important genetic contributions. In a previous transmission disequilibrium study in which 75 complete trios were included, single-nucleotide polymorphisms (SNPs) in serotoninergic and GABAergic genes were associated with early-onset OCD. Our aim was to assess those findings in an extended collection of early-onset OCD trios. METHODS: A transmission disequilibrium test for SNPs in HTR1B (rs2000292), SLC18A1 (rs6586896), GAD1 (rs3791860), and GAD2 (rs8190748) was performed in a total of 101 early-onset OCD trios, from which 26 trios were newly recruited for the purpose of the present analysis. RESULTS: All the SNPs were overtransmitted from parents to OCD probands (p < 0.012, significant after Bonferroni correction). CONCLUSIONS: These results are consistent with the previous findings and constitute more evidence of the role of genetic factors related to serotoninergic and GABAergic pathways in the pathophysiology of early-onset OCD.

Genetic variability in the serotoninergic system and age of onset in anorexia nervosa and obsessive-compulsive disorder.

The age of onset of some psychiatric disorders may have etiopathogenic and clinical effects and may influence outcome. Following on from previous work by our group where we showed that early onset anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) shared a common genetic background, the aim of the present study is to assess genetic pleiotropy related to the serotonergic system (SLC6A4, 5HTR2A, 5HTR2C, TPH2, SLC18A1), in a common phenotype such as very-early age of onset. One hundred and sixteen adolescents diagnosed with AN and 74 adolescents diagnosed with OCD participated in the present study. We confirmed the existence of a genetic overlap between OCD and AN. Specifically, we described genetic pleiotropy for age at onset across these disorders, associating two SNPs (rs6311, rs4942587) of the HTR2A with the very-early onset phenotype.

Functional MRI with a set-shifting task in adolescent anorexia nervosa: A cross-sectional and follow-up study.

Studies of set-shifting in adolescent AN present conflicting results, since not all have found differences with regard to controls. To date, no functional Magnetic Resonance Imaging (fMRI) studies have been carried out in adolescent patients, nor have patients been assessed after weight recovery. In this study, 30 female AN patients aged 12-17 and 16 matched control subjects were assessed both at baseline and after six months and renutrition using a structured diagnostic interview, clinical and neurocognitive scales, and fMRI during a set-shifting task. Adolescent AN patients presented similar performance on different neurocognitive tests and also on a set-shifting task during fMRI, but they showed a lower activation in the inferior and middle occipital and lingual gyri, fusiform gyri and cerebellum during the set-shifting task. No correlations were found between decreased activation and clinical variables such as body mass index, eating or depressive symptoms. After six months of treatment and renutrition in AN patients, there were no differences between patients and controls. These results show that adolescent AN patients have lower activation in relevant brain areas during a set-shifting task, and support the use of fMRI with set-shifting paradigms as a biomarker in future studies.

Adolescent anorexia nervosa: cross-sectional and follow-up frontal gray matter disturbances detected with proton magnetic resonance spectroscopy.

There are very few magnetic resonance spectroscopy studies in anorexia nervosa and none of them with young adolescent patients. We studied 12 anorexia nervosa (DSM-IV) patients aged 11-17 consecutively admitted to an Eating Disorders Unit. An evaluation with laboratory data, psychopathological scales, magnetic resonance spectroscopy ((1)H MRS) and a neuropsychological battery was carried out at admission and after 7 months' follow-up and weight recovery. Psychopathological and neuropsychological and MRS examinations were also performed in 12 control subjects. In the MRS study at the frontal gray matter, the anorexic group had a significantly lower N-acetyl-aspartate (NAA) (p = .002), glutamate/glutamine (Glx) (p = .010) and myo-Inositol (mI) (p = .022) than the control group. The NAA correlated positive and significantly with triiodothyronin (Rho = .64) and the estimate level of intelligence measured with the vocabulary subtest of the WISC-R (Rho=.64). There were also positive correlations with body mass index (Rho = .47) and with attention measured with the coding subtest of the WISC-R (Rho=.51) and negative with loss of weight (Rho = -.51) but they were not statistically significant. At follow-up, there was an increase in body mass index (p=.002), triiodothyronin (p = .005), and insulin-like growth factor 1 (p = .017) and a decrease in cortisol (p = .005). In the MRS a significant increase (p = .013) in NAA was observed. The conclusion would be that NAA, Glx and mI are low in the frontal gray matter of adolescents with anorexia nervosa and specially NAA correlates with some nutritional and cognitive parameters. These alterations seem to be reversible in young patients.

Association of regulatory TPH2 polymorphisms with higher reduction in depressive symptoms in children and adolescents treated with fluoxetine.

Genetic variability related to the brain serotonergic system has a significant impact on both the susceptibility to psychiatric disorders, such as major depressive disorder (MDD), and the response to antidepressant drugs, such as fluoxetine. TPH2 is one of the most important serotonergic candidate genes in selective serotonin reuptake inhibitors (SSRIs) pharmacogenetic studies. The aim of the present study was to evaluate the influence of regulatory polymorphisms that are specifically located in human TPH2 transcription factor binding sites (TFBSs), and therefore could be functional by altering gene expression, on clinical improvement in children and adolescents treated with fluoxetine. The selection of SNPs was also based on their linkage disequilibrium with TPH2 rs4570625, a genetic variant with questionable functionality, which was previously associated with clinical response in our pediatric population. A total of 83 children and adolescents were clinically evaluated 12weeks after initiating antidepressant treatment with fluoxetine for the first time. Clinical improvement was assessed by reductions in depressive symptoms measured using the Children's Depression Inventory (CDI) scale. The polymorphisms rs11179002, rs60032326 and rs34517220 were, for the first time in the literature, significantly associated with higher clinical improvement. The strongest association was found for rs34517220. In particular, minor allele homozygotes showed higher score reductions on the CDI scale compared with the major allele carriers. Interestingly, this polymorphism is located in a human TPH2 TFBS for two relevant transcription factors in the serotoninergic neurons, Foxa1 and Foxa2, which together with the high level of significance found for this SNP, could indicate that rs34517220 is in fact the crucial functional genetic variant related to the fluoxetine response. These results provide new evidence for the role of regulatory genetic variants that could modulate human TPH2 expression in the SSRI antidepressant response.

Epigenetic and genetic variants in the HTR1B gene and clinical improvement in children and adolescents treated with fluoxetine.

The serotonin 1B receptor (5-HT1B) is important to both the pathogenesis of major depressive disorder and the antidepressant effects of selective serotonin reuptake inhibitors. Although fluoxetine has been shown to be effective and safe in children and adolescents, not all patients experience a proper clinical response, which has led to further study into the main factors involved in this inter-individual variability. Our aim was to study the effect of epigenetic and genetic factors that could affect 5-hydroxytryptamine receptor 1B (HTR1B) gene expression, and thereby response to fluoxetine. A total of 83 children and adolescents were clinically assessed 12weeks after of initiating an antidepressant treatment with fluoxetine for the first time. We evaluated the influence of single nucleotide polymorphisms (SNPs) specifically located in transcription factor binding sites (TFBSs) on their clinical improvement. A combined genetic analysis considering the significant SNPs together with the functional variant rs130058 previously associated in our population was also performed. Moreover, we assessed, for the first time in the literature, whether methylation levels of the HTR1B promoter region could be associated with the pharmacological response. Two, rs9361233 and rs9361235, were significantly associated with clinical improvement after treatment with fluoxetine. The heterozygous genotype combination analysis showed a negative correlation with clinical improvement. The lowest improvement was experienced by patients who were heterozygous for all three SNPs. Moreover, a negative correlation was found between clinical improvement and the average methylation level of the HTR1B promoter. These results give new evidence for the role of epigenetic and genetic factors which could modulate HTR1B expression in the pharmacological response to antidepressants.