Therapeutic outcome and long-term naturalistic follow-up of female adolescent outpatients with AN: clinical, personality and psychopathology evolution, process indicators and outcome predictors.

BACKGROUND: Anorexia nervosa (AN) is a serious mental illness of growing prevalence in childhood and adolescence. Despite its severity, there are still no completely satisfactory evidence-based treatments. Follow-up studies represent the most effective attempt to enlighten treatment effectiveness, outcome predictors and process indicators. METHODS: Seventy-three female participants affected with AN were assessed at intake (T0) and at 6 (T1) and 12 (T2) months of an outpatient multimodal treatment program. Nineteen participants were assessed 15 years after discharge (T3). Changes in diagnostic criteria were compared with the chi-square test. Clinical, personality and psychopathology evolution were tested with ANOVA for repeated measures, using the t-test or Wilcoxon test as post-hoc. T0 features among dropout, stable and healed participants were compared. Healed and unhealed groups at long-term follow-up were compared using Mann-Whitney U test. Treatment changes were correlated to each other and with intake features using multivariate regression. RESULTS: The rate of complete remission was 64.4% at T2, and 73.7% at T3. 22% of participants maintained a full diagnosis at T2, and only 15.8% at T3. BMI significantly increased at each time-point. A significant decrease of persistence and increase in self-directedness were evidenced between T0 and T2. Interoceptive awareness, drive to thinness, impulsivity, parent-rated, and adolescent-rated general psychopathology significantly decreased after treatment. Lower reward dependence and lower cooperativeness characterized the dropout group. The healed group displayed lower adolescent-rated aggressive and externalizing symptoms, and lower parent-rated delinquent behaviors. BMI, personality and psychopathology changes were related with each other and with BMI, personality and psychopathology at intake. CONCLUSION: A 12-months outpatient multimodal treatment encompassing psychiatric, nutritional and psychological approaches is an effective approach for the treatment of mild to moderate AN in adolescence. Treatment was associated not only with increased BMI but also with positive personality development, and changes in both eating and general psychopathology. Lower relational abilities may be an obstacle to healing. Approaches to treatment resistance should be personalized according to these finding.

Clinical and personality characteristics of adolescents with anorexia nervosa with or without non-suicidal self-injurious behavior.

PURPOSE: About one-fifth of patients with anorexia nervosa (AN) engage in non-suicidal self-injury (NSSI). This study examined clinical and temperament profile of female adolescents with both disorders (AN+NSSI) as compared with peers with AN only. METHODS: A consecutive sample of 73 female adolescents with AN (mean age: 13.77 years), who had been admitted to inpatient or day-hospital services, received clinical, cognitive, and temperament/character evaluations. Of them, 32 met DSM-5 criteria also for NSSI. Assessments included demographics, standard nutrition parameters, Youth Self-Report (YSR), Wechsler Intelligence Scale for Children IV (WISC-IV), Temperament and Character Inventory (TCI), and Global Assessment of Functioning (GAF). RESULTS: No differences were detected between AN+NSSI and AN in demographics, body mass index, or age at onset of AN. AN+NSSI had higher rate of binging and purging, higher YSR scores for both internalizing and externalizing psychopathology, lower total IQ, and lower Self-directedness and Cooperativeness scores. CONCLUSIONS: These data suggest that adolescents with AN+NSSI have psychopathological, cognitive and overall character features that differ from patients with AN only. These characteristics may have implications for treatment and outcome.

Succinic semialdehyde dehydrogenase deficiency: The combination of a novel ALDH5A1 gene mutation and a missense SNP strongly affects SSADH enzyme activity and stability.

Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive metabolic disorder of GABA catabolism. SSADH is a mitochondrial homotetrameric enzyme encoded by ALDH5A1 gene. We report the molecular characterization of ALDH5A1 gene in an Italian SSADHD patient, showing heterozygosity for four missense mutations: c.526G>A (p.G176R), c.538C>T (p.H180Y), c.709G>T (p.A237S) and c.1267A>T (p.T423S), the latter never described so far. The patient inherited c.526A in cis with c.538T from the mother and c.709T in cis with c.1267T from the father. To explore the effects of the two allelic arrangements on SSADH activity and protein level, wild type, single or double mutated cDNA constructs were expressed in a cell system. The p.G176R change, alone or in combination with p.H180Y, causes the abolishment of enzyme activity. Western blot analysis showed a strongly reduced amount of the p.176R-p.180Y double mutant protein, suggesting increased degradation. Indeed, in silico analyses confirmed high instability of this mutant homotetramer. Enzyme activity relative to the other p.423S-p.237S double mutant is around 30% of wt. Further in silico analyses on all the possible combinations of mutant monomers suggest the lowest stability for the tetramer constituted by p.176R-p.180Y monomers and the highest stability for that constituted by p.237S-p.423S monomers. The present study shows that when a common SNP, associated with a slight reduction of SSADH activity, is inherited in cis with a mutation showing no consequences on the enzyme function, the activity is strongly affected. In conclusion, the peculiar arrangement of four missense mutations occurring in this patient is responsible for the SSADHD phenotype.

Personality subtypes in adolescents with anorexia nervosa.

The aims of this study are to (1) empirically identify the personality subtypes of adolescents with anorexic disorders and (2) investigate the personality disorders, identity disturbances, and affective features associated with the different subtypes. We assessed 102 adolescent patients with Eating Disorders (anorexia nervosa and eating disorder not otherwise specified) using three clinical instruments: the Shedler-Westen Assessment Procedure for Adolescents (SWAP-200-A) (Westen D, Shedler J, Durrett C, Glass S, Martens A. Personality diagnoses in adolescence: DSM-IV Axis II diagnoses and an empirically derived alternative. Am J Psychiatry 2003;160:952-966), the Affective Regulation and Experience Questionnaire (AREQ) (Zittel Conklin C, Bradley R, Westen D. Affect regulation in borderline personality disorder. J Nerv Ment Dis 2006;194:69-77), and the Identity Disorder Questionnaire (IDQ) (Wilkinson-Ryan T, Westen D. Identity disturbance in borderline personality disorder: An empirical investigation. Am J Psychiatry 2000;157:528-541). We performed a Q factor analysis of the SWAP-200-A descriptions of our sample to identify personality subtypes. We correlated these personality styles with AREQ and IDQ factors and explored the personality differences among individuals with the different types of ED. The Q factor analysis identified three personality subtypes: high-functioning/perfectionist, emotionally dysregulated, and overcontrolled/constricted. Each subtype showed specific identity and affective features, comorbidities with different personality disorders, and clinical implications. These results contribute to the understanding of adolescents with ED and seem to be relevant for treatment planning.