Francesca Neri

Decreased whole-blood global DNA methylation is related to serum hormones in anorexia nervosa adolescents

Abstract Objectives. The one-carbon metabolism, also known as methionine-homocysteine cycle, governs the dynamics of DNA methylation, epigenetically regulating gene expression, and has been reported altered in anorexia nervosa (AN) adult patients. The aim of this study consisted in assessing whole-blood DNA methylation in adolescent AN patients, assessing its significance in relationship to clinical and hormonal variables. Methods. Whole-blood global DNA methylation was measured as incorporation of [3H]dCTP following HpaII cut in 32 adolescent females affected by restrictive type AN and compared to 13 healthy controls. Homocysteine, vitamin B12 and folate plasma levels were assessed as well as fasting plasma levels of leptin and steroid hormones. Clinical variables, including severity and associate states and traits, were assessed by means of the EDI-3, CDI and STAI-Y scales. Results. We confirm that whole-blood global DNA methylation is modestly albeit significantly reduced in AN adolescents with respect to controls, correlating with plasma leptin and steroid hormone levels. Conversely, clinical traits did not correlate with the outcome variable. Conclusions. A better definition of the epigenetic dysregulation underlying AN pathology or vulnerability might lead to develop useful markers for diagnosis, prognostic classification and tailored therapeutic interventions in these vulnerable patients since the earliest phases of their disease.

Impact of speed and magnitude of weight loss on the development of brain trophic changes in adolescents with anorexia nervosa: a case control study

BackgroundAnorexia nervosa commonly arises during adolescence and is associated with more than one medical morbidity. Abnormalities in brain structure (defined as “pseudoatrophy”) are common in adolescents with anorexia nervosa; however, their correlations with endocrinological profiles and clinical parameters are still unclear. In particular, no study has described the impact of BMI (body mass index) variations (speed and magnitude of weight loss) on cerebral trophism changes.MethodsEleven adolescents with anorexia nervosa and 8 healthy controls underwent cerebral MRI (magnetic resonance imaging) examination to obtain global and partial volumes (gray matter, white matter and cerebrospinal fluid) and clinical evaluation. The Mann-Whitney U test was used to compare partial volumes and clinical variables between cases and controls. The Spearman non-parametric test was performed in order to explore correlations between the variables studied.ResultsThe patients diagnosed with AN showed significantly increased cerebrospinal fluid (CSF) volumes and decreased total gray (GM) and white matter (WM) volumes. The degree of weight loss (deltaBMI) correlated inversely with the GM volume; the increase of CSF compartment correlated directly with the rapidity of weight loss (DeltaBMI/disease duration).ConclusionsThis study suggests a correlation between cerebral alterations in AN and the speed and magnitude of weight loss, and outlines its importance for the therapeutic treatment.

Autobiographical memory in adolescent girls with anorexia nervosa.

OBJECTIVE The aim of the study is to investigate deficits in autobiographical memory in adolescents with anorexia nervosa (AN). METHODS Sixty female individuals with AN and 60 healthy volunteers with an age range of 11-18 years were enrolled. The Autobiographical Memory Test (AMT), the Eating Disorder Inventory-3, the Toronto Alexithymia Scale-20 for the evaluation of alexithymia and Childrens Depression Inventory to evaluate depressive traits were administered. In addition to classical AMT words, we proposed seven experimental cues, chosen from words often used by individuals with eating disorders in daily life. RESULTS Girls with AN showed a massive overgeneral memory effect. This effect was not related to the presence of depression or alexithymia but increased with the duration of the disorder rather than with its severity. DISCUSSION The alteration of autobiographical memory manifests in adolescence. Girls with AN showed a dysregulation of both negative and positive emotional experiences that seemed to be influenced by the disease duration.

Autobiographical memory in adolescent girls with anorexia nervosa

OBJECTIVE The aim of the study is to investigate deficits in autobiographical memory in adolescents with anorexia nervosa (AN). METHODS Sixty female individuals with AN and 60 healthy volunteers with an age range of 11-18 years were enrolled. The Autobiographical Memory Test (AMT), the Eating Disorder Inventory-3, the Toronto Alexithymia Scale-20 for the evaluation of alexithymia and Childrens Depression Inventory to evaluate depressive traits were administered. In addition to classical AMT words, we proposed seven experimental cues, chosen from words often used by individuals with eating disorders in daily life. RESULTS Girls with AN showed a massive overgeneral memory effect. This effect was not related to the presence of depression or alexithymia but increased with the duration of the disorder rather than with its severity. DISCUSSION The alteration of autobiographical memory manifests in adolescence. Girls with AN showed a dysregulation of both negative and positive emotional experiences that seemed to be influenced by the disease duration.

Mathematical Difficulties in Nonverbal Learning Disability or Co-Morbid Dyscalculia and Dyslexia

The main goal of the present study was to shed further light on the weaknesses of children with different profiles of mathematical difficulties, testing children with nonverbal learning disability (NLD), co-morbid dyscalculia and dyslexia (D&D), or typical development (TD). Sixteen children with NLD, 15 with D&D, and 16 with TD completed tasks derived from Butterworth (2003) and divided into: a capacity subscale (i.e., a number–dots comparison task, a number comparison task, and a dots comparison task); and an achievement subscale (i.e., mental calculations and arithmetical fact retrieval). Children with NLD were impaired in the dots comparison task, children with D&D in the mental calculation and arithmetical facts.

Neuroligand binding endophenotypes in blood cells distinguish two subsets of borderline personality disorder patients.

Neurotransmitter ligand binding in blood cells was assessed in borderline personality disorder (BDP) patients, testing the possibility that different biochemical endophenotypes might lie beneath a specific clinical presentation. The density of peripheral benzodiazepine receptors (PBR) and serotonin transporters were assessed in peripheral blood mononuclear cells (PBMC) and platelets, respectively, showing a decrease of both parameters. Moreover, a further significant decrease of PBR in PBMC was shown for those patients with a depressive trait. Further confirmation of the presence of different molecular endophenotypes underlying the dissimilar clinical presentations in BPD may advance our possibility of successfully treating these patients.

Reduced fasting plasma levels of diazepam-binding inhibitor in adolescents with anorexia nervosa.

OBJECTIVE Altered expression and/or function, both peripherally and centrally, of various neuropeptides is involved in the neurophysiology of anorexia nervosa (AN). Diazepam-binding inhibitor (DBI) is an interesting peptide for understanding this crosstalk. The aim of this work was to assess fasting plasma levels of DBI and leptin in patients with AN. METHOD Twenty-four AN adolescents were recruited together with 10 age-comparable healthy controls. Neuropeptide determinations were performed on plasma samples by enzyme-linked immunosorbent assays. Patients with AN were further characterized for the presence of a depressive state or anxiety by using, respectively, the Childrens Depression Inventory or the State-Trait Anxiety Inventory form Y. RESULTS Levels of both plasma DBI and leptin were reduced in patients with AN (∼40 and ∼70%, respectively). DBI levels displayed a tendency to increase in the presence of a depressive state, although not with anxiety, whereas leptin levels correlated exclusively with body mass index. DISCUSSION These data further extend our knowledge of neuropeptide dysfunction in AN, and plasma DBI may represent a marker for this disease, in particular considering its correlation with comorbid mood disorders.

Paradoxical increase of plasma vitamin B12 and folates with disease severity in anorexia nervosa

OBJECTIVE Anorexia nervosa (AN) is a complex disorder involving severe psychological manifestations and multiple organ damage, including liver dysfunction. The primary aim of this study consisted in assessing plasma levels of vitamin B12 and folates with respect to liver function enzymes considering the liver-storage properties of this vitamin. METHOD We recruited 70 restrictive type AN adolescents and the severity of psychopathological traits was assessed using EDI-3 scale. Plasma levels of vitamin B12 , folates, transaminases (AST, ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP) and cholinesterase (CHE) were determined. RESULTS About 38.5% of patients displayed vitamin B12 values (H-B12) above the upper range of normal reference; 4.3% of patients had increased values of folates; 20 and 11.4% of patients displayed ALT and AST values above reference limits; none had GGT values above normal range. Albeit low CHE and ALP values were found in 55 and 20% of patients, respectively, a linear correlation with both transaminases was present only for vitamin B12 and folates; furthermore, H-B12 patients had both higher AST and ALT values. EDI- 3 subscores significantly correlated with vitamin B12 and folates plasma values and H-B12 patients displayed EDI-3 higher values. DISCUSSION These data suggest that plasma levels of vitamin B12 might be an early marker of liver dysfunction, possibly also related to more severe psychopathological aspects. The identification of patients with higher fasting plasma vitamin B12 levels could therefore lead to earlier and more careful refeeding interventions. Further studies will clarify the potential role of this vitamin in AN clinical practice.

Diazepam Binding Inhibitor and Dehydroepiandrosterone Sulphate Plasma Levels in Borderline Personality Disorder Adolescents

Background: Borderline personality disorder (BPD) patients display a complex and heterogeneous clinical phenotype that plausibly implies variable underlying pathogenic mechanisms. A dysregulation of peripheral benzodiazepine receptors has previously been shown in BPD peripheral tissues, implying possible alterations of its ligand, the diazepam binding inhibitor (DBI) or of the downstream products of its activation, i.e. neuroactive steroids. Methods: The aim of this work consisted in assessing, by ELISA, fasting plasma levels of DBI and dehydroepiandrosterone sulphate (DHEA-S), including cortisol and the cortisol-to-DHEA-S molar ratio (CDR), in 17 BPD adolescents versus 13 healthy controls, testing the possibility that clinical scales related to depressive or anxious traits (CDI, STAI-Y) or to disease severity (BPDCL) might be associated with a selective dysregulation of these parameters. Results: DBI plasma levels were unchanged, while DHEA-S ones were significantly increased (approx. 70%) and the CDR decreased in BPD patients. No meaningful correlations with clinical variables emerged. Conclusion: Our results indicate that a dysfunction of the neurosteroid system might be operative in BPD in spite of unchanged DBI plasma levels and that DHEA-S might represent a generalized trait marker for the altered stress response that is associated with this disorder.

19q12q13.2 duplication syndrome: neuropsychiatric long-term follow-up of a new case and literature update

Genetic syndromes are well characterized by the phenotypic point of view, but little is known about their progression and patients’ quality of life. We report a 10-year neuropsychiatric follow-up of a boy with duplication of chromosome 19. Cytogenetic investigation was requested at the age of 5 years for psychomotor and speech delay. The genomic study identified an 8.17 Mb duplication on chromosome 19q12q13.2. We propose that the long-term follow-up of our patient would help to delineate the neuropsychiatric phenotype associated with 19q duplication. This study could be a model for further long-term research in the neuropsychiatric follow-up of patients with 19q duplication syndrome.