PCSK9 and leptin plasma levels in anorexia nervosa.

AIM: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of low-density-lipoprotein cholesterol (LDL-C), a major risk factor for cardiovascular (CV) disease. Since the hormone leptin has been suggested as having a role in CV risk regulation, possibly by modulating LDL receptor expression through the PCSK9 pathway, nutritional status may represent a potential regulator. Thus, evaluation of PCSK9 levels in human eating disorders appears to be of interest. In this report, we evaluate the lipoprotein profile, PCSK9, and leptin levels in subjects affected by anorexia nervosa (AN) to improve our understanding of the metabolic alterations in this disease. METHODS AND RESULTS: We designed a case-control observational study, enrolling 20 anorexic adolescent females and 20 adolescent females without AN as the control group, age- and sex-matched. Subjects affected by AN showed lower BMI, total cholesterol, and LDL-C in comparison to the control group, with lipoprotein levels in the normal range. Furthermore, adolescent girls with AN show significantly higher PCSK9 (+24%, p < 0.005) and lower leptin levels (-43%, p < 0.01), compared to the control group. CONCLUSIONS: The findings of increased levels of PCSK9 and reduced leptin levels among AN subjects warrant further research in order to unravel the role of the liver and adipose tissue in the management of PCSK9/LDL metabolism in adolescents affected by AN.

Bodily self-recognition and body size overestimation in restrictive anorexia nervosa: implicit and explicit mechanisms.

It is widely known that among others, a pervasive symptom characterizing anorexia nervosa (AN) concerns body image overestimation, which largely contributes to the onset and maintenance of eating disorders. In the present study, we investigated the nature of the body image distortion by recording accuracy and reaction times in both a group of healthy controls and AN patients during two validated tasks requiring an implicit or explicit recognition of self/other hand stimuli, in which the perceived size of the stimuli was manipulated. Our results showed that (1) the perceived size of hand stimuli modulated both the implicit and explicit processing of body parts in both groups; (2) the implicit self-advantage emerged in both groups, but the bodily self, at an explicit level (perceptual, psycho-affective, cognitive) together with the integration and the distinction between self and other, was altered only in restrictive anorexia patients. Although further investigations will be necessary, these findings shed new light on the relationship between the different layers of self-experience and bodily self-disorders.

Horticultural Therapy May Reduce Psychological and Physiological Stress in Adolescents with Anorexia Nervosa: A Pilot Study.

Studies in psychiatric populations have found a positive effect of Horticultural therapy (HCT) on reductions in stress levels. The main objective of the present pilot study was to evaluate the impact of the addition of HCT to conventional clinical treatment (Treatment as Usual, TaU) in a sample of six female adolescents with anorexia nervosa restricting type (AN-R), as compared to six AN-R patients, matched for sex and age, under TaU only. This is a prospective, non-profit, pilot study on patients with a previous diagnosis of AN-R and BMI < 16, recruited in 2020 in clinical settings. At enrolment (T0) and after treatment completion (TF), psychiatric assessment was performed. At T0, all the patients underwent: baseline electrocardiogram acquisition with a wearable chest strap for recording heart rate and its variability; skin conductance registration and thermal mapping of the individual's face. An olfactory identification test was administered both to evaluate the olfactory sensoriality and to assess the induced stress. One-way analyses of variance (ANOVAs) were performed to analyze modifications in clinical and physiological variables, considering time (T0, TF) as a within-subjects factor and group (experimental vs. control) as between-subjects factors. When the ANOVA was significant, post hoc analysis was performed by Paired Sample T-tests. Only in the HCT group, stress response levels, as measured by the biological parameters, improved over time. The body uneasiness level and the affective problem measures displayed a significant improvement in the HCT subjects. HCT seems to have a positive influence on stress levels in AN-R.

Anorexia Nervosa, Body Image Perception and Virtual Reality Therapeutic Applications: State of the Art and Operational Proposal.

Anorexia Nervosa (AN) patients exhibit distorted body representation. The purpose of this study was to explore studies that analyze virtual reality (VR) applications, related to body image issues, to propose a new tool in this field. We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, Scopus, and Web of Science databases were explored; the review included 25 studies. Research has increased over the last five years. The selected studies, clinical observational studies (n = 16), mostly concerning patients' population with AN (n = 14) or eating disorders (EDs) diagnosis, presented multiple designs, populations involved, and procedures. Some of these studies included healthy control groups (n = 7). Studies on community sample populations were also selected if oriented toward clinical applications (n = 9). The VR technologies in the examined period (about 20 years) have evolved significantly, going from very complex and bulky systems, requiring very powerful computers, to agile systems. The advent of low-cost VR devices has given a big boost to research works. Moreover, the operational proposal that emerges from this work supports the use of biofeedback techniques aimed at evaluating the results of therapeutic interventions in the treatment of adolescent patients diagnosed with AN.

Feeding disorders in preschoolers: a short-term outcome study in an Italian Family Care Program.

PURPOSE: To provide a description about a cohort of preschoolers with feeding disorders (FD) recruited from the therapeutic nursery "Cerco Asilo" of a tertiary care University Hospital, and to evaluate the short-term clinical outcome after 6 months of multidisciplinary treatment. METHODS: The present inception cohort study was based on an observational longitudinal research design comparing families who underwent the multidisciplinary treatment and those who did not. 42 children (47.6% female; 52.4% males-mean age 36.7 months, SD 17.2, range 2.3-65 months) underwent FD assessment according to the DC-0-3R diagnostic criteria (T0). At the end of the assessment, 62% of families with FD children agreed to be included in the family-based treatment. Both treated and untreated children with FD underwent a follow-up clinical evaluation after 6 months (T1) from baseline. Comparison of clinical features at T0 between groups of subjects resolving or not the FD was performed. To evaluate baseline factors associated with FD resolution, principal components analysis (PCA) was used to identify new synthetic variables that were then used in a logistics analysis. Moreover, clinical differences between T1 and T0 were compared with a t test. RESULTS: Two third of the cases (66.7%) resolved the FD, while one third (33.3%) did not. Children who had the FD resolved displayed at T0 significant differences in clinical features with respect to those who did not. Specifically, the FD subtype Feeding Disorder of Caregiver-Infant Reciprocity was strongly associated with resolution, while the subtype Infantile Anorexia was not. In addition, the component depicting "Anxious-Depressed", "Mood" and "Isolation" problems was independently associated with a significantly higher probability of resolution, similar to children having FD other than anorexia. CONCLUSIONS: FD in preschoolers are associated with problems in emotional development and in the relationship with parents. These difficulties tend to accentuate if the disorder persists. The study suggests the need to investigate the maintaining factors of FD in preschool age. LEVEL OF EVIDENCE: Level IV: Evidence obtained from multiple time series with and without the intervention.

Autonomic Nervous System Response during Light Physical Activity in Adolescents with Anorexia Nervosa Measured by Wearable Devices.

Anorexia nervosa (AN) is associated with a wide range of disturbances of the autonomic nervous system. The aim of the present study was to monitor the heart rate (HR) and the heart rate variability (HRV) during light physical activity in a group of adolescent girls with AN and in age-matched controls using a wearable, minimally obtrusive device. For the study, we enrolled a sample of 23 adolescents with AN and 17 controls. After performing a 12-lead electrocardiogram and echocardiography, we used a wearable device to record a one-lead electrocardiogram for 5 min at baseline for 5 min during light physical exercise (Task) and for 5 min during recovery. From the recording, we extracted HR and HRV indices. Among subjects with AN, the HR increased at task and decreased at recovery, whereas among controls it did not change between the test phases. HRV features showed a different trend between the two groups, with an increased low-to-high frequency ratio (LF/HF) in the AN group due to increased LF and decreased HF, differently from controls that, otherwise, slightly increased their standard deviation of NN intervals (SDNN) and the root mean square of successive differences (RMSSD). The response in the AN group during the task as compared to that of healthy adolescents suggests a possible sympathetic activation or parasympathetic withdrawal, differently from controls. This result could be related to the low energy availability associated to the excessive loss of fat and lean mass in subjects with AN, that could drive to autonomic imbalance even during light physical activity.

Autistic traits impact on olfactory processing in adolescent girls with Anorexia Nervosa restricting type.

The correct functioning of the chemosensory pathway is pivotal for the attitude towards feeding. In some neuropsychiatric disorders, abnormalities of the sensory processing dramatically affect feeding behavior; however, evidences for an olfactory involvement in Anorexia Nervosa (AN) are still controversial. We administered a complete olfactory testing battery, the Sniffin' Sticks Extended Test, to a cohort of 19 girls with Restrictive Anorexia Nervosa (AN-R) and 19 healthy controls. A battery of questionnaires aiming to evaluate eating attitude, psychopathologic disorders and autistic traits was also administered. No difference was found between the two groups in any of the olfactory tasks. Despite the lack of correlation between olfaction and disease severity, however, olfactory performances were related to autistic traits in anorectic girls (r = -0.489, p = 0.039). Girls with AN-R do not appear to have an impaired olfactory function with respect to controls. However, a possible correlation between olfactory ability and autistic traits was discovered. In light of such findings, the role of possible relations between social functioning-related features and olfactory processing in AN-R is discussed.

Excessive physical activity in young girls with restrictive-type anorexia nervosa: its role on cardiac structure and performance.

PURPOSE: The aim of this study was to investigate the influence of hyperactivity on left ventricular mass (LVM) in Anorexia Nervosa restricting-type (AN-R) and the correlation between LVM and auxologic parameters/circulating hormones. METHODS: Echocardiography was performed in 44 AN-R girls, subgrouped in 24 hyperactive (ANH+) and 20 non-hyperactive (ANH-), and in 20 controls (HC). LVM indexed to Body Surface Area (LVMi) and LVM indexed to height (LVMh) were calculated. RESULTS: LVMi and LVMh were significantly lower in the AN-R subjects compared to HC. Moreover, both LVMi and LVMh were higher in the ANH+ than in the ANH-. In the HC, LVMi was higher when compared to the ANH- subjects than to the ANH+. Stepwise analysis revealed that in the ANH+ group, fT4 was the only independent predictor of LVMh, while in the ANH- group, height was the only independent predictors of LVMi. CONCLUSIONS: Despite its negative influence on disease severity and outcome, hyperactivity from the standpoint of cardiac function makes the LVM of AN-R young girls more similar to HC. LEVEL OF EVIDENCE: Level III, case-control study.

Interoception and Autonomic Correlates during Social Interactions. Implications for Anorexia.

The aim of this study is to investigate the bodily-self in Restrictive Anorexia, focusing on two basic aspects related to the bodily self: autonomic strategies in social behavior, in which others' social desirability features, and social cues (e.g., gaze) are modulated, and interoception (i.e., the sensitivity to stimuli originating inside the body). Furthermore, since previous studies carried out on healthy individuals found that interoception seems to contribute to the autonomic regulation of social behavior, as measured by Respiratory Sinus Arrhythmia (RSA), we aimed to explore this link in anorexia patients, whose ability to perceive their bodily signal seems to be impaired. To this purpose, we compared a group of anorexia patients (ANg; restrictive type) with a group of Healthy Controls (HCg) for RSA responses during both a resting state and a social proxemics task, for their explicit judgments of comfort in social distances during a behavioral proxemics task, and for their Interoceptive Accuracy (IA). The results showed that ANg displayed significantly lower social disposition and a flattened autonomic reactivity during the proxemics task, irrespective of the presence of others' socially desirable features or social cues. Moreover, unlike HCg, the autonomic arousal of ANg did not guide behavioral judgments of social distances. Finally, IA was strictly related to social disposition in both groups, but with opposite trends in ANg. We conclude that autonomic imbalance and its altered relationship with interoception might have a crucial role in anorexia disturbances.

Altered exposure-related reshaping of body appreciation in adolescent patients with anorexia nervosa.

Several studies suggest a relation between repeated exposure to extremely thin bodies in media and the perceptual and emotional disturbances of body representation in anorexia nervosa (AN). In this study, we utilized an exposure paradigm to investigate how perceptual experience modulates body appreciation in adolescents with AN as compared to healthy adolescents. Twenty AN patients and 20 healthy controls were exposed to pictures of thin or round models and were then required to express liking judgments about bodies of variable weight. Brief exposure to round models increased the liking judgments of round bodies but not those of thin bodies in healthy adolescents. Furthermore, exposure to round models increased the liking judgments of both thin and round bodies in adolescents with AN. Patients did not show any change of liking judgments after exposure to thin models. These results point to weak norm-based reshaping of body appreciation in AN patients.

Parent-child Interaction Treatment for Preschoolers with Feeding Disorders.

BACKGROUND: This study examined the immediate outcome of Feeding Disorders (FD) in preschoolers referred to the family treatment program Cerco Asilo. METHOD: 21 children (mean age [SD=1]: 39 months [1]; range 9-65 months) with a diagnosis of FD were included in the treatment for 24 weeks. Specifically, seven subjects were diagnosed with Infantile Anorexia (IA), nine subjects with Sensory Food Aversion (SFA), and five subjects with Feeding Disorder of Caregiver-Infant Reciprocity (FDCIR). RESULTS: The great majority of patients with SFA and with FDCIR resolved the FD, whereas children with IA did not respond well to the treatment. LIMITATIONS: The study's main limitations are the relatively small sample size, and the lack of a control group. CONCLUSIONS: Findings suggest that changes in the parentchild relationship could generally promote FD resolution, other than IA. These data may have implications for clinical practice suggesting the need to develop ad hoc intervention protocols tailored to children with IA and their families.

The impact of internalizing symptoms on autistic traits in adolescents with restrictive anorexia nervosa.

BACKGROUND: Although previous studies indicated a positive association between restrictive anorexia-nervosa (AN-R) and autistic traits, the potential interference of psychiatric internalizing comorbidity on this association is not yet fully investigated. MATERIALS AND METHODS: The aim of this study was to explore autistic traits and internalizing psychopathology in adolescents (age range: 11.7-17.2 years) with AN-R. Twenty-five patients referred to two tertiary-care hospitals were compared to a large control group (N=170) with no differences in age and sex. AN-R patients and controls filled out instruments assessing autistic traits (autism spectrum quotient [AQ]), psychopathology (youth self-report [YSR] 11-18), and eating patterns (eating attitude test [EAT]). In order to disentangle the possible mediating role of internalizing symptoms on autistic traits, two separate control groups (called True and False healthy control, both composed of 25 eating-problem-free participants) were derived from the whole control group on the basis of the presence or absence of internalizing problems in the YSR. RESULTS: AN-R patients scored significantly higher on AQ compared to the whole control group and to controls without internalizing problems (True HC), but these differences disappeared when only controls with internalizing problems (False HC) were considered. CONCLUSION: Autistic traits in AN-R individuals may have been overestimated and may partly be due to comorbid internalizing symptoms in investigated patients.

The role of wearable sensors and wireless technologies for the assessment of heart rate variability in anorexia nervosa.

PURPOSE: Bradycardia and abnormal cardiac autonomic function are related to increased mortality in anorexia nervosa (AN). The aim of this study was to assess heart rate (HR) and HR variability of young adolescents with AN as compared to controls by means of wearable sensors and wireless technologies. METHOD: The ECG signal was recorded in 27 AN girls and 15 healthy girls at rest using a wearable chest strap. The tachogram, the mean intervals between R peaks (meanRR), the root mean square of successive differences (RMSSD), the power of low-frequency (LF) and high-frequency (HF) bands and the LF/HF ratio were assessed. RESULTS: All AN girls showed a reduced HR and an increased meanRR and RMSSD. An HF increase, a LF decrease, and a LF/HF reduction indicated a prevalence of the parasympathetic on sympathetic activity. CONCLUSIONS: The instruments used in this pilot study were feasible, unobtrusive and extremely suitable in AN subjects who are burdened by high incidence of cardiovascular mortality; their application could open to new approaches of vital signs monitoring in hospitals as well as in home settings.

Growth impairment and growth hormone-IGF-1 axis in infantile anorexia nervosa.

BACKGROUND: Infantile anorexia nervosa (AN) is a specific eating disorder of prepubertal children. Poor data are available on growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis in this disorder. PATIENT REPORT: We report on a boy (4.5 years) with progressive growth impairment. At psychiatric assessment (DC: 0-3 R, AXIS I), he fulfilled all required criteria for diagnosis of infantile AN. Endocrine evaluation suggested impaired peripheral response to GH (high GH and low IGF-1 levels), likely related to energy deficiency. METHODS: Auxological evaluation was shown as raw data and SDS using Italian reference values. GH secretion was assessed by arginine provocative test; IGFI generation test was done administering recombinant GH (0.05 mg/kg/day for four days). Psychiatric assessment was performed according to the DC:0-3R protocol. CONCLUSION: Impaired GH-IGF-1 axis may be involved in growth delay of children with infantile AN. A strict collaboration between endocrine pediatricians and child psychiatrists is advisable in the assessment of poor growing children without recognizable organic causes, showing normal/high GH levels and low IGF-1 values.

Assessment of mental disorders in preschoolers: the multiaxial profiles of diagnostic classification 0-3.

A group of 291 preschoolers consecutively enrolled at the Early Childhood Mental Health Service of IRCSS Stella Maris (Italy) were assessed using the Diagnostic Classification Zero to Three (DC:0-3; ZERO TO THREE, 1994). All active variables were extracted from its five axes, and a multiple correspondence analysis was performed. This analysis evidenced four multiaxial clinical profiles: (a) Multisystem developmental disorders (Axis I) were correlated with the underinvolved quality of relationship (Axis II), medical conditions (Axis III), and a low level of emotional functioning (Axis V); (b) regulatory disorders (Axis I) were correlated with maladaptive or angry/hostile relationship (Axis II), medical conditions (Axis III), and an immature level of emotional functioning (Axis V); (c) affective disorders (Axis I) were correlated with anxious/tense relationship (Axis II), stress factors (Axis IV), and emotional functioning vulnerable to stress (Axis V); and (d) adjustment, feeding, and sleeping disorders (Axis I) were correlated with mild relationship disorders (Axis II) and important impact of stress factors (Axis IV). These findings support DC:0-3 as a valid tool to detect multiaxial profiles that could be useful to plan comprehensive treatments of the disorders.

Selective cognitive empathy deficit in adolescents with restrictive anorexia nervosa.

BACKGROUND: A growing, but conflicting body of literature suggests altered empathic abilities in subjects with anorexia nervosa-restricting type (AN-R). This study aims to characterize the cognitive and affective empathic profiles of adolescents with purely AN-R. METHODS: As part of a standardized clinical and research protocol, the Interpersonal Reactivity Index (IRI), a valid and reliable self-reported instrument to measure empathy, was administered to 32 female adolescents with AN-R and in 41 healthy controls (HC) comparisons, matched for age and gender. Correlational analyses were performed to evaluate the links between empathy scores and psychopathological measures. RESULTS: Patients scored significantly lower than HC on cognitive empathy (CE), while they did not differ from controls on affective empathy (AE). The deficit in CE was not related to either disease severity nor was it related to associated psychopathology. CONCLUSION: These results, albeit preliminary, suggest that a dysfunctional pattern of CE capacity may be a stable trait of AN-R that should be taken into account not only for the clinical management, but also in preventive and therapeutic intervention.

Do parentese prosody and fathers' involvement in interacting facilitate social interaction in infants who later develop autism?

BACKGROUND: Whether development of autism impacts the interactive process between an infant and his/her parents remains an unexplored issue. METHODOLOGY AND PRINCIPAL FINDINGS: Using computational analysis taking into account synchronic behaviors and emotional prosody (parentese), we assessed the course of infants' responses to parents' type of speech in home movies from typically developing (TD) infants and infants who will subsequently develop autism aged less than 18 months. Our findings indicate: that parentese was significantly associated with infant responses to parental vocalizations involving orientation towards other people and with infant receptive behaviours; that parents of infants developing autism displayed more intense solicitations that were rich in parentese; that fathers of infants developing autism spoke to their infants more than fathers of TD infants; and that fathers' vocalizations were significantly associated with intersubjective responses and active behaviours in infants who subsequently developed autism. CONCLUSION: The parents of infants who will later develop autism change their interactive pattern of behaviour by both increasing parentese and father's involvement in interacting with infants; both are significantly associated with infant's social responses. We stress the possible therapeutic implications of these findings and its implication for Dean Falk's theory regarding pre-linguistic evolution in early hominins.

Child Behavior Check List 1½-5 as a tool to identify toddlers with autism spectrum disorders: a case-control study.

Tools to identify toddlers with autism in clinical settings have been recently developed. This study evaluated the sensitivity and specificity of the Child Behavior Check List 1½-5 (CBCL 1½-5) in the detection of toddlers subsequently diagnosed with an Autism Spectrum Disorder (ASD), ages 18-36 months. The CBCL of 47 children with ASD were compared to the CBCL of 47 toddlers with Other Psychiatric Disorders (OPD) as well as the CBCL of 47 toddlers with Typical Development (TD) in a case control study. One-way analysis of variance (ANOVA) and logistic regression with odds ratio (OR) analyses were performed. In order to establish the optimal threshold able to discriminate children with ASD from children with OPD and TD, Receiver Operating Characteristic (ROC) analyses were performed. One-way ANOVA revealed significant differences between the three groups. Logistic regression analysis showed that the Withdrawn and the Pervasive Developmental Problems (PDP) subscales can recognize toddlers subsequently identified as ASD from both children with TD (p<0.001) and OPD (p<0.001). ROC analyses showed very high sensitivity and specificity for the PDP (0.98 and 0.91) and Withdrawn (0.92 and 0.97) subscales when ASD was compared to TD. Sensitivity and specificity of Withdrawn (0.90 and 0.83) and PDP (0.85 and 0.83) remained high when comparing ASD versus OPD. In conclusion, the CBCL 1½-5 seemed to be able to identify toddlers subsequently diagnosed with ASD from children with TD and OPD. Its high sensitivity and specificity, coupled with its efficiency in terms of time and cost, suggest this broadband tool should be tested in a pilot screening survey of toddlers in the general population.

Neuropsychological functioning in children and adolescents with restrictive-type anorexia nervosa: an in-depth investigation with NEPSY-II.

Several studies have investigated the neuropsychological functioning of patients with anorexia nervosa restrictive type (AN-r), but results are conflicting. Here we compared the neuropsychological profile of 23 female children and adolescents with AN-r and of 46 typical controls (aged 9-16 years) using the second edition of the NEPSY (a Developmental Neuropsychology Assessment) neuropsychological battery. AN-r patients presented subtle cognitive flexibility impairments in audiomotor responses (p = .033). Conversely, superior performance in verbal fluency (p = .024) and memory (p = .034) was observed only in AN-r patients with an associated unipolar mood disorder. This profile of marginally impaired and enhanced performance was independent from illness duration and starvation degree, suggesting that it may preexist and represent a vulnerability factor for the disease onset.

Do parents recognize autistic deviant behavior long before diagnosis? Taking into account interaction using computational methods.

BACKGROUND: To assess whether taking into account interaction synchrony would help to better differentiate autism (AD) from intellectual disability (ID) and typical development (TD) in family home movies of infants aged less than 18 months, we used computational methods. METHODOLOGY AND PRINCIPAL FINDINGS: First, we analyzed interactive sequences extracted from home movies of children with AD (N = 15), ID (N = 12), or TD (N = 15) through the Infant and Caregiver Behavior Scale (ICBS). Second, discrete behaviors between baby (BB) and Care Giver (CG) co-occurring in less than 3 seconds were selected as single interactive patterns (or dyadic events) for analysis of the two directions of interaction (CG→BB and BB→CG) by group and semester. To do so, we used a Markov assumption, a Generalized Linear Mixed Model, and non negative matrix factorization. Compared to TD children, BBs with AD exhibit a growing deviant development of interactive patterns whereas those with ID rather show an initial delay of development. Parents of AD and ID do not differ very much from parents of TD when responding to their child. However, when initiating interaction, parents use more touching and regulation up behaviors as early as the first semester. CONCLUSION: When studying interactive patterns, deviant autistic behaviors appear before 18 months. Parents seem to feel the lack of interactive initiative and responsiveness of their babies and try to increasingly supply soliciting behaviors. Thus we stress that credence should be given to parents' intuition as they recognize, long before diagnosis, the pathological process through the interactive pattern with their child.