Impact of emotional abuse on eating disorder psychopathology: A multiple mediation analysis.

INTRODUCTION: Childhood maltreatment, particularly emotional abuse (EA), has been identified as a significant risk factor for the development of eating disorders (EDs). This study investigated the association between EA and ED symptoms while considering multiple potential mediators. METHODS: Participants included 151 individuals with Anorexia Nervosa (AN), 115 with Bulimia Nervosa (BN), and 108 healthy controls. The Childhood trauma questionnaire, the Toronto Alexithymia scale, the Behavioral inhibition System, and the Eating Disorder Inventory 2 scale were completed before treatment. A mediator path model was conducted in each group: EA was set as independent variable, eating symptoms as dependent variables and ineffectiveness, sensitivity to punishment, alexithymia, and impulsivity as mediators. RESULTS: In individuals with AN, impulsivity emerged as a significant mediator between EA and desire for thinness and bulimic behaviors. Conversely, in individuals with BN, sensitivity to punishment was found to mediate the association between EA and dissatisfaction with one's body. Ineffectiveness and difficulty identifying emotions were identified as transdiagnostic mediators in both clinical groups. No mediation effect was found in healthy individuals. DISCUSSION: The simultaneous assessment of multiple mediators in a unique model outlines the complex interplay between childhood EA and ED psychopathology. Improving ineffectiveness, emotion identification, sensitivity to punishment and impulsivity and exploring their relations with early emotional abuse may represent treatment targets in individuals with EDs and childhood trauma.

The bidirectional connection between family functioning and psychopathology: A network analysis in a large sample of adolescents with anorexia nervosa and their parents.

Family functioning is a risk and maintaining factor for anorexia nervosa (AN). This study aims to identify specific areas of family functioning according to adolescents and parental perspectives associated with eating and general psychological symptoms in people with AN. Four-hundred-forty-five adolescents with AN or atypical AN and their parents were enrolled. Adolescents completed the Eating Disorder Inventory-3, the Youth Self-Report questionnaire, and the Family Assessment Device (FAD). Their parents filled in the FAD. A network analysis was conducted including all subscales. The bridge function analysis was applied to identify the bridge nodes connecting each community constituted of family functioning perception with the communities of adolescents' eating and general psychological symptoms. Family communication was the node most strongly connecting fathers and mothers' perception of family functioning and adolescents' eating symptoms. Problem solving was the node with the highest bridge expected influence between mothers' family functioning and adolescents' general psychopathology. General functioning and problem solving were the bridge nodes between adolescents' view of family functioning and eating and general psychopathology. Maturity fear, interpersonal insecurity, and interpersonal alienation were the bridge nodes between adolescents' eating symptoms and mothers, fathers, and adolescents' family functioning communities respectively. Family members must be involved in the therapeutic process to improve family communication and problem solving diverting their attention toward emotional needs and interpersonal difficulties of adolescents with AN. Developing autonomy and independence from parents and building trustworthy relationships with peers may be favored by improving familiar dynamics and may contribute to prevent the maintenance of AN.

Mediation role of interpersonal problems between insecure attachment and eating disorder psychopathology.

PURPOSE: Although insecure attachment and interpersonal problems have been acknowledged as risk and maintaining factors of eating disorders (EDs), the mediating role of interpersonal problems between attachment style and ED psychopathology has been poorly explored. The purpose of this study was to investigate the mediating role of interpersonal problems between insecure attachment and ED psychopathology. METHODS: One-hundred-nine women with anorexia nervosa and 157 women with bulimia nervosa filled in the Eating Disorder Inventory-2 (EDI-2) and the Experiences in Close Relationships (ECR) revised scale to assess ED core symptoms and attachment styles, respectively. Interpersonal difficulties were evaluated by the Inventory of Interpersonal Problems (IIP-32). A mediator's path model was conducted with anxious and avoidant attachment subscores as independent variables, ED core symptoms as dependent variables and interpersonal difficulties as mediators. The diagnosis was entered in the model as a confounding factor. RESULTS: The socially inhibited/avoidant interpersonal dimension was a mediator between avoidant attachment and the drive to thinness as well as between avoidant attachment and body dissatisfaction. An indirect connection was found between attachment-related anxiety and bulimic symptoms through the mediation of intrusive/needy score. CONCLUSIONS: Social avoidance and intrusiveness mediate the relationships between avoidant and anxious attachment styles and ED psychopathology. These interpersonal problems may represent specific targets for psychotherapeutic treatments in individuals with EDs and insecure attachment. LEVEL OF EVIDENCE: Level III: Evidence obtained from well-designed cohort or case-control analytic studies.

Pathways between childhood maltreatment and life satisfaction in adolescents with eating disorders: A network analysis.

OBJECTIVE: This study explored the association between Childhood maltreatment (CM) experiences and life satisfaction in adolescents with eating disorders (EDs). METHODS: Adolescent inpatients with EDs completed the Childhood Trauma Questionnaire, the Satisfaction With Life Scale, the Brief Symptom Inventory and the Eating Disorder Inventory-2 at admission (n = 361) and discharge (n = 354). A network analysis was conducted to identify the shortest pathways between different types of CM and life satisfaction at admission and discharge. RESULTS: General psychopathology, life satisfaction, and ED symptoms improved from admission to discharge. At admission, emotional abuse and emotional neglect were included in the pathway between sexual/physical abuse and life satisfaction. Emotional neglect was directly connected with life satisfaction while emotional abuse was connected through feeling disliked by others, feelings of inferiority and worthlessness. At discharge, only the direct negative connection between emotional neglect and perception of excellent conditions in the life persisted. CONCLUSIONS: Emotional maltreatment experiences and general psychopathology, but not disordered eating symptoms, are involved in the association between sexual/physical CM and life satisfaction in adolescents with EDs. Emotional neglect may affect life satisfaction regardless of symptoms severity. These findings inform clinicians for assessment and treatment of maltreated adolescents with EDs.

Emotional non-acceptance mediates the relationship between insecure attachment and specific psychopathology in women with eating disorders.

OBJECTIVE: Insecure attachment is considered a general risk factor for eating disorders (ED). Emotion dysregulation has been proposed as one of the possible mechanisms by which attachment insecurity may affect ED psychopathology. Aim of the present study was to investigate whether difficulties in acceptance of emotions or emotional clarity may mediate the connection between insecure attachment and ED psychopathology. METHOD: One hundred and twenty patients participated and completed the Italian version of Eating Disorder Inventory-2, Experience in Close Relationship questionnaire and Difficulties in Emotion Regulation Scale. A mediator path model was performed, in which insecure attachment dimensions were set as independent variables, ED specific psychopathology measures as dependent variables, and non-acceptance of emotion and lack of emotional clarity as mediators. RESULTS: The association between both attachment avoidance and anxiety and ED specific symptoms was mediated by emotional non-acceptance, but not by emotional clarity. CONCLUSIONS: This study showed the importance to address emotion regulation in individuals with ED, focussing on improving emotional acceptance. Exploring early developmental processes which lead to non-acceptance of emotions could improve this psychological trait in people with ED.

COVID-19 Pandemic and Eating Disorders: What Can We Learn About Psychopathology and Treatment? A Systematic Review.

PURPOSE OF REVIEW: This systematic review aims to collect evidence regarding the impact of the SarsCov-2 pandemic on people affected by eating disorders (EDs) targeting the following variables: psychopathology changes, mechanisms of vulnerability or resilience, and perception of treatment modifications during the pandemic. RECENT FINDINGS: Since the beginning of the pandemic, a mental health deterioration has been detected in the general population and especially in people affected by pre-existing psychiatric conditions. Furthermore, mental healthcare has moved toward online treatment. ED people showed a trend toward worsening of ED-specific psychopathology and impairment in general psychopathology. The most common vulnerability mechanisms were social isolation and feelings of uncertainty, while heightened self-care and reduced social pressure were resilience factors. The online treatment, although raising many concerns related to its quality, was considered the best alternative to the face-to-face approach. These findings may support the idea that stressful events contribute to the exacerbation of ED psychopathology and highlight the relevance of internalizing symptoms in EDs. The identification of putative risk and resilience variables as well as of subjective factors affecting online treatment perception may inform healthcare professionals and may promote more personalized approaches.

Emotional traumatic experiences significantly contribute to identify a maltreated ecophenotype sub-group in eating disorders: Experimental evidence.

OBJECTIVE: Eating disorders (EDs) are associated with a high prevalence of childhood maltreatment (CM). We aimed to experimentally assess if people with EDs and history of CM show altered biological, emotional and behavioural responses to the Trier Social Stress Test (TSST). METHODS: According to Childhood Trauma Questionnaire cut-off scores, 29 participants (14 with anorexia nervosa [AN] and 15 with bulimia nervosa [BN]) were classified as maltreated (Mal) ED participants while 19 participants (11 with AN and eight with BN) without CM were identified as no maltreated (noMal) ED participants. Cortisol, anxiety and hunger responses to TSST and post-stress body dissatisfaction were measured. RESULTS: Mal ED people showed heightened emotional reactivity, lower levels of hunger and more severe post-stress body dissatisfaction in comparison with noMal ones. Higher cortisol production was observed in people with AN, regardless of CM history, and in those with BN and emotional CM. Emotional trauma was the main CM type contributing to the experimental differences observed in Mal ED people. CONCLUSIONS: This is the first study providing experimental and multi-level support to the maltreated ecophenoptype hypothesis in people with EDs. These findings may promote new insights into the biological bases of EDs and provide novel therapeutic implications.

Risk and resilience factors for specific and general psychopathology worsening in people with Eating Disorders during COVID-19 pandemic: a retrospective Italian multicentre study.

PURPOSE: The COVID-19 pandemic restrictions had negative impact on the psychopathology of people with Eating Disorders (EDs). Factors involved in the vulnerability to stressful events have been under-investigated in this population. We aimed to assess which factors contributed to COVID-19-induced worsening in both general and specific psychopathology. METHODS: Three-hundred and twelve people with a clinically defined diagnosis of an ED and undergoing a specialist ED treatment in different Italian ED services before the spreading of COVID-19 pandemic filled in an online survey. ED specific and general psychopathology changes after COVID-19 quarantine were retrospectively evaluated. Factors related to COVID-19 concerns (financial condition, fear of contagion, perceived social isolation/support, satisfaction in peer, family or sentimental relationships), illness duration and treatment-related variables (type of treatment provided, type of access to care, satisfaction with therapeutic relationships) were included as predicting factors in a structural equational model, which included latent variables consisting of general and ED psychopathology items as outcomes. RESULTS: A perceived low quality of therapeutic relationships, fear of contagion and increased isolation were positively associated with psychopathology worsening. Reduced satisfaction with family and with friends' relationships and reduced perceived social support were associated with ED and general symptoms deterioration, respectively. No significant effect emerged for intimate relationships, illness duration, economic condition and type of treatment. CONCLUSIONS: This study provides a comprehensive evaluation of clinical variables associated with psychopathological changes during the COVID-19 lockdown period highlighting potential risk and resilience factors and, possibly, informing treatment as well as prevention strategies for EDs. LEVEL OF EVIDENCE IV: Evidence obtained from multiple time series analysis such as case studies.

Attitudes and gaps in knowledge of the diagnosis, treatment, and psychopathology of eating disorders among different health professionals.

BACKGROUND: Health professionals from different specialties in medical and psychological areas play an important role in diagnosis and treatment of eating disorders (EDs). This study aimed to identify gaps in knowledge about the diagnosis, etiology, and management of EDs and to assess health professionals' attitudes towards these illnesses. METHODS: A new questionnaire was developed and validated. Residents and consultants working in disciplines involved in the management of EDs (namely, internal medicine, general practitioners, psychiatric area, psychological area, and surgical area) completed the questionnaire. Knowledge and attitudes were compared among the study groups through one-way ANCOVA and chi-square tests. RESULTS: The final version of the questionnaire consisted of 54 items assessing the following areas: stigma, treatment, physical complications, diagnosis, and aetiopathogenesis of EDs. For all health professionals the area of most deficiency was the aetiopathogenesis, while the best one was the management of physical complications. All medical professionals showed less knowledge than psychiatrists in terms of etiology, diagnosis, and treatment of EDs. A lack of knowledge about evidence-based psychotherapies, general psychopathology, and family members' role in the management of EDs emerged among all health professionals. Stigma was found among non-mental health professionals who considered these patients to be different from others and responsible for their abnormal eating behaviors. CONCLUSIONS: Clarifying the health professionals' specific gaps occurring in the knowledge of EDs and in the attitudes towards these individuals may inform educational programs to improve early detection and management of EDs.

This article investigated attitudes towards individuals with eating disorders (EDs) and knowledge of the diagnosis and management of these illnesses among health professionals. A gap in the knowledge of diagnosis, aetiopathogenesis, and treatment emerged above all in non-mental health professionals. Psychotherapy effectiveness and the role of family members in the therapeutic process were not sufficiently acknowledged, and general psychological factors contributing to the onset of EDs were not recognized. Impaired attitudes were primarily observed among surgeons, although all health professionals considered these disorders as distinct from others and viewed these individuals as responsible for their abnormal eating behaviors. These findings outline a type of stigma towards EDs that is associated with health professionals and may impair early diagnosis and recovery. Educational programs should aim to provide continuous education to update and improve the knowledge of EDs among health professionals.

Childhood maltreatment, alexithymia and eating disorder psychopathology: A mediation model.

BACKGROUND: The relationship between childhood maltreatment and eating disorder psychopathology has been under-investigated. OBJECTIVE: The purpose of this study was to investigate the role of alexithymia in mediating the relationship between childhood maltreatment experiences and eating disorder (ED) symptoms. PARTICIPANTS AND SETTING: One-hundred-forty-three women with anorexia nervosa, 110 women with bulimia nervosa and 108 healthy women filled in the Eating Disorder Inventory-2, the Childhood Trauma Questionnaire and the Toronto Alexithymia Scale-20 (TAS-20). METHODS: A mediator path model including childhood trauma types as predictors, the subscales of the TAS-20 as mediators and ED specific symptoms as dependent variables was conducted in individuals with EDs and in healthy women. RESULTS: In women with EDs emotional abuse was directly associated with body dissatisfaction and was associated to drive to thinness, bulimia and body dissatisfaction through the mediation of difficulties to identify emotions. In healthy women, physical neglect was directly associated to drive to thinness and bulimia, but no significant mediation effect through alexithymia emerged. CONCLUSION: Impaired emotion recognition mediates the association between childhood emotional abuse and ED symptoms. Individuals with early emotional abuse may experience ED symptoms to manage confused emotional perceptions. Improving emotional understanding and acceptance may be a treatment target in early maltreated individuals with EDs.

The interplay between emotion regulation, interpersonal problems and eating symptoms in individuals with obesity: A network analysis study.

INTRODUCTION: A complex and bidirectional relationship between eating and psychological symptoms in individuals with obesity has been proposed. This study aims to identify the specific processes playing a role in this association, using a data-driven approach. METHODS: Two hundred ninety-four adults with obesity, including 106 (36 %) with binge-eating disorder, were consecutively admitted to a specialized public center. They completed self-report questionnaires to assess emotion regulation, interpersonal problems, self-esteem, binge-eating symptoms, and expectancies regarding eating behaviors. To assess the interplay among eating and psychological variables, a network analysis was used. The bridge function analysis was also performed to identify the bridge nodes among three communities (eating symptoms, interpersonal and emotional problems). RESULTS: The network was stable. Limited access to emotion regulation strategies, eating helps manage negative affect, and non-assertiveness were the nodes with the highest strength centrality. Lack of emotional clarity, non-assertiveness, socially inhibition, and binge-eating were the nodes with the highest bridge strength. LIMITATIONS: The main limitation of the study is the cross-sectional nature of the findings which prevents to infer causality regarding the association between symptoms in the network. DISCUSSION: An interplay between eating symptoms and affective and interpersonal factors characterizes individuals with obesity. Across the variety of psychological problems associated with obesity, the present study suggests specific psychological variables and their connections that could be addressed to improve treatment outcome.

Pathways to eating disorder care: A European multicenter study.

BACKGROUND: The aim of this study was to assess barriers and facilitators in the pathways toward specialist care for eating disorders (EDs). METHODS: Eleven ED services located in seven European countries recruited patients with an ED. Clinicians administered an adapted version of the World Health Organization "Encounter Form," a standardized tool to assess the pathways to care. The unadjusted overall time needed to access the ED unit was described using the Kaplan-Meier curve. RESULTS: Four-hundred-nine patients were recruited. The median time between the onset of the current ED episode and the access to a specialized ED care was 2 years. Most of the participants did not directly access the specialist ED unit: primary "points of access" to care were mental health professionals and general practitioners. The involvement of different health professionals in the pathway, seeking help for general psychiatric symptoms, and lack of support from family members were associated with delayed access to ED units. CONCLUSIONS: Educational programs aiming to promote early diagnosis and treatment for EDs should pay particular attention to general practitioners, in addition to mental health professionals, and family members to increase awareness of these illnesses and of their treatment initiation process.

Using network analysis to explore the association between eating disorders symptoms and aggressiveness in Bulimia nervosa.

Aggressive behaviors have been reported to be more frequent in people with eating disorders (ED), especially bulimia nervosa (BN). Network Analysis (NA) is particularly useful or examining the interactions among symptoms of comorbid conditions through the identification of "bridge symptoms," defined as those symptoms playing a key role in the connection between two syndromic clusters. The aim of the present study was to investigate the association of ED core symptoms and ED-related psychopathology with aggressiveness in a clinical sample of women with BN through NA. Two hundred and seventy-nine women with BN completed the Eating Disorder Inventory-2 and the Buss-Durkee Hostility Inventory. A NA was conducted, including ED symptoms and aggressiveness measures. The bridge function was implied to identify symptoms bridging ED symptoms and aggressiveness. The most connected nodes among communities were asceticism and impulsivity from ED-related psychopathology, drive for thinness from ED-core psychopathology and guilt and suspicion from aggressiveness domain. In particular, drive for thinness connected ED-core community to verbal hostility, while impulsivity connected ED-related symptoms to guilt and suspicion of aggressiveness community. In conclusion the present study showed that in people with BN guilt is the specific negative emotion of the hostile dimensions that may be bidirectionally associated with ED symptoms.

Adult attachment style and salivary alpha-amylase and emotional responses to a psychosocial stressor in women with eating disorders.

BACKGROUND: The fine-tuning of the endogenous stress response system, which includes the hypothalamus-pituitary-adrenal axis and the sympathetic nervous system (SNS), is influenced by early attachment relationships. A higher prevalence of insecure attachment has been detected in people with eating disorders (EDs). Thus, we investigated the emotional and the SNS reactivity to the Trier Social Stress Test (TSST) in women with EDs in relation to their attachment profiles. METHODS: Fifty women with EDs and 20 healthy women participated into an experimental study. Attachment was evaluated by Experience in Close Relationship questionnaire. Salivary α-amylase (sAA) levels were measured to assess the SNS reactivity to TSST while the emotional response was measured by the STAI state scale. RESULTS: Compared to women with EDs and low attachment anxiety and healthy controls, women with EDs and high attachment anxiety showed lower TSST-induced sAA production without difference in anxiety scores. Women with EDs and high attachment avoidance showed similar sAA response to TSST but higher levels of anxiety scores compared to those with low attachment avoidance and healthy controls. CONCLUSIONS: Our findings corroborate the idea that adult attachment may be associated with variability in emotional and biological responses to a psychosocial stressor in women with EDs.

Trends in the Incidence and Antibiotic Resistance of Enterococcal Bloodstream Isolates: A 7-Year Retrospective Multicenter Epidemiological Study in Italy.

The spread of resistance to vancomycin and other last-resort drugs in Enterococcus spp. remains of concern. In Italy, surveillance data for enterococcal bloodstream isolates in humans are scant. The aim of our study was to assess the incidence trends of bacteremias due to Enterococcus species and their prevalence trends of antimicrobial resistance. We retrospectively included all consecutive not-duplicate Enterococcus species isolated from blood cultures, in patients from 11 Italian hospitals (2011-2017). Incidence was defined as the number of isolates per 10,000 patient-days, while resistance prevalence was defined as the number of resistant strains divided by the number of tested strains. We included 4,858 isolates (59%, 36%, and 5% due to Enterococcus faecalis, E. faecium, and other Enterococcus spp., respectively). Over the study period, the incidence of bacteremias due to E. faecalis (incidence rate ratio [IRR]: 1.02, 95% confidence interval [CI]: 1.00-1.04, p = 0.008) and E. faecium increased (IRR: 1.03, 95% CI: 1.01-1.05, p < 0.001) alongside with the whole enterococcal bacteremias trend (IRR: 1.02, 95% CIs: 1.01-1.04, p = 0.002). A progressive increase in vancomycin-resistant E. faecium (VREfm) bacteremias was observed. Resistance to tigecycline and linezolid was rarely reported. The incidence of enterococcal bloodstream isolates is increasing in Italy, together with the prevalence of VREfm. Resistance to linezolid, a cornerstone drug used in the treatment of VRE bloodstream infection, remains negligible.

The impact of COVID-19 lockdown and of the following "re-opening" period on specific and general psychopathology in people with Eating Disorders: the emergent role of internalizing symptoms.

BACKGROUND: We assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on specific Eating Disorder (ED) and general psychopathology in people with an ED diagnosis during the lockdown period and after the end of the related containment measures. METHODS: People with clinically defined diagnosis and undergoing treatment for an ED completed an online survey, which included adapted questions from standardized psychometric scales. Data relative to three different time periods (before, during and after the end of lockdown) were collected. Psychopathological changes over these periods were investigated and compared through one-way analysis of variance or covariance with repeated measures. RESULTS: Three hundred twelve people completed the survey (57.4% diagnosed with Anorexia Nervosa (AN) or atypical AN, 20.2% with Bulimia Nervosa, 15.4% with Binge Eating Disorder, 7.05% with Other Specified Feeding or Eating Disorders). The severity of both specific and general psychopathology increased during the lockdown and the rise of general symptoms persisted in the following re-opening phase, except for suicide ideation. Almost all of these findings were not affected by ED diagnosis, participants' age and illness duration. LIMITATIONS: The retrospective nature of data collection is the main limitation of the study. CONCLUSIONS: People with EDs showed a COVID-19 emergency-induced worsening of both general and specific psychopathology. The effect on general psychopathology persisted in the re-opening period. These findings suggest a high stress vulnerability of ED individuals with important effects on internalizing symptoms, which are worth of attention by clinicians.

Comparison of Serum Total Valproic Acid Levels and %CDT Values in Chronic Alcohol Addictive Patients in an Italian Clinic: A Retrospective Study.

BACKGROUND: Valproate is a broad-spectrum anticonvulsant that is effective in the treatment of tonic-clonic, myoclonic and absence seizures as well as in partial seizures as a second-line drug. It has been widely demonstrated in the literature that the effect of valproate on type-A γ-aminobutyric acid (GABA-A) receptors may reduce relapse to ethanol abuse. This retrospective study evaluated a 3-year period in which 42 patients from the Department of Alcoholism and Substance Abuse (DASA) were treated with valproate. OBJECTIVES: We compared different serum total valproic acid (VPA) concentrations, and the effectiveness of this drug in maintaining alcohol abstinence was evaluated by percentage of carbohydrate deficient transferrin (%CDT) values. METHOD: CDT is a biochemical marker used for identifying regular high alcohol consumption and monitoring abstinence in outpatients during treatment. Serum concentrations of valproate were divided into four groups: <10, 10-30, 31-50, and >50 µg/mL. RESULTS: This study shows that a mean serum total VPA concentration >30 µg/mL is more effective in maintaining alcohol abstinence than a lower one (p < 0.05). In this study, mean serum total VPA concentrations between 31 and 50 µg/mL showed the same effectiveness as higher ones (>50 µg/mL); in fact, there was no significant difference in mean %CDT values between these two groups (p > 0.05). After at least 12 months' treatment with valproate, mean platelet counts increased by 12 × 103/µL compared with baseline (254 ± 63 vs 242 × 103/µL, p > 0.05, respectively) in patients with mean serum total VPA levels <10 µg/mL; increased by 8 × 103/µL from baseline (253 ± 59 vs 245 × 103/µL, p > 0.05, respectively) in patients with levels between 10 and 30 µg/mL; decreased by 2 × 103/µL from baseline (265 ± 63 vs 267 × 103/µL, p > 0.05, respectively) in patients with levels between 31 and 50 µg/mL, and decreased by 48 × 103/µL from baseline (215 ± 56 vs 263 × 103/µL, p < 0.05, respectively) in patients with levels >50 µg/mL. CONCLUSION: A mean serum total concentration lower than the currently accepted therapeutic level (50-100 µg/mL) may have the same effectiveness in maintaining alcohol abstinence with a lower risk of presenting side effects.

Role of folic acid depletion on homocysteine serum level in children and adolescents with epilepsy and different MTHFR C677T genotypes.

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. An elevated total plasma Hcy concentration (tHcy) is a risk factor for vascular disease. The present study aimed to assess the role of antiepileptic drugs (AEDs) and C677T methylenetetrahydrofolate (MTHFR) polymorphisms on tHcy in pediatric patients with epilepsy treated for at least 6 months with various treatment regimens protocols including the newer AEDs. The study group was recruited from children and adolescents with epilepsy followed up in the Child Neuropsychiatry Clinic of the Second University of Naples, between January 2007 and March 2008. Inclusion criteria were: (1) patients with epilepsy, treated with one or more anticonvulsant drugs for at least 6 months; (2) age between 2 and 16 years. Plasma tHcy concentrations were considered elevated when they exceeded 10.4 µmol/L, and folate concentrations <3 ng/mL were considered deficient. Serum vitamin B12 levels were considered normal between 230 and 1,200 pg/mL. The study group was composed of 78 patients (35 males, 43 females), aged between 3 and 15 years (mean 8.9 years). Thirty-five patients were taking AED monotherapy, 43 polytherapy. Sixty-three healthy sex- and age-matched children and adolescents served as controls. The mean tHcy value in the patient group was higher than the mean value in the control group (12.11 ± 7.68 µmol/L vs 7.4±4.01 µmol/L; p<0.01). DNA analysis for the MTHFR C677T polymorphism showed the CT genotype in 46%, CC in 35% and TT in 17.8% of cases. Decreased folic acid serum levels significantly correlated with increased tHcy levels (p<0.003). Female sex was a less significant risk factor for increased tHcy levels (p=0.039). Our study confirms the association between hyperhomocysteinemia and epilepsy. The elevation of tHcy is essentially related to low folate levels. Correction of poor folate status, through supplementation, remains the most effective approach to normalize tHcy levels in patients on AED mono- or polytherapy.