Role of parental educational level as psychosocial factor in a sample of inpatients with anorexia nervosa and bulimia nervosa.

Introduction: Evidence on parental educational level (PEL) as a risk factor for Eating Disorders (EDs) is mixed, and no study has assessed its role in relation to the compliance and outcomes of treatments in EDs. Further, no study differentiated from the educational level of mothers and fathers, nor considered the possible mediation of perfectionism in fostering EDs. Methods: A clinical sample of 242 first-ever admitted inpatients with EDs provided information on PEL and completed the following questionnaires: the Eating Disorder Examination Questionnaire (EDE-Q) and the Frost Multidimensional Perfectionism Scale (F-MPS). Clinicians also provided information on the Hamilton Rating Scale for Anxiety (HAM-A) and the Hamilton Rating Scale for Depression (HAM-D) for each participant. Results: Individuals with high PEL (whether mothers, fathers, or both parents) showed significantly higher scores on depressive symptoms and lower on parental criticism, were younger, had an earlier age of onset, had fewer years of illness, more were students and employed, and fewer had offspring. Individuals with fathers or both parents with high educational levels suffered more from Anorexia Nervosa rather than Bulimia Nervosa, had a longer length of stay during the current hospitalization, had less dietary restraint, and had higher personal standards. Individuals with mothers with high educational levels showed a lower rate of previous substance or alcohol addiction. Personal standards partially mediated the relationship between higher PEL and lower dietary restraint. Discussion: PEL emerged to be a twofold psychosocial risk factor, being associated with higher depressive symptoms and a longer length of stay, but also with a shorter duration of illness and better scholar and working involvement. Higher PEL was related to higher personal standards but not to global perfectionism. Patterns of eating psychopathology emerged based on the high PEL of mothers or fathers.

Perfectionism in anorexia nervosa: Associations with clinical picture and personality traits.

Although many researchers addressed the topics, no consistent data are currently available regarding the relationship between perfectionism and personality traits in anorexia nervosa (AN). The present study aimed to assess differences between high- and low-perfectionism groups of patients with AN and to identify which variables show the strongest association with perfectionism. A group of inpatients with AN (n = 193) was recruited and completed a battery of self-report questionnaires regarding eating-related and general psychopathology, perfectionism, and personality. On the basis of perfectionism scores, patients were divided into high- and low-perfectionism groups. High-perfectionist patients displayed higher eating-related and general psychopathology; higher depressive, cyclothymic, irritable and anxious temperament, and lower self-directedness, cooperativeness and self-esteem. Perfectionism was associated with the drive for thinness, cooperativeness, self-esteem and anxious temperament. On the basis of the two personality traits most strongly correlated with perfectionism (i.e., cooperativeness and anxious temperament), patients could be correctly assigned to the high- or low-perfectionism group by an algorithm. The study suggests that perfectionism in AN is related to eating psychopathology, especially of restrictive type, and personality features such as cooperativeness and anxious temperament. These findings confirm the important role of perfectionism in AN, not only concerning eating behaviour but personality as well.

Anorexia Nervosa and Somatoform Dissociation: A Neglected Body-Centered Perspective.

Dissociation in anorexia nervosa (AN) is common (literature reported 29% of dissociative disorders in eating disorders) and higher in patients with binge-purging AN (BP-AN) than in those with restricter AN (R-AN). However, the distinction between somatoform (SomD) and psychoform dissociation (PsyD) is understudied. We aimed to assess the differences in PsyD and SomD, eating-related, general, and body-related psychopathology, and childhood trauma between subtypes of AN. Then, we attempted to describe a subgroup of patients with AN with marked SomD comparing them to patients without SomD, also controlling the results for PsyD and AN subtypes. Inpatients with AN (n = 111; 109 women and 2 men) completed self-reported questionnaires evaluating dissociation, eating-related, body-related, and general psychopathology, and childhood abuses. Patients with BP-AN reported higher SomD and PsyD and a more severe clinical picture than those with R-AN. The SomD-group (n = 41) showed higher eating concerns, trait-anxiety, body-related variables, and sexual/physical abuse compared to the no-SomD group (n = 70), independently of AN subtype and PsyD symptoms. Results described particular features of patients with AN and SomD. Data, clinically, suggest a careful assessment, for both SomD and PsyD, especially when a history of bodily-impacting trauma is present, potentially fostering dissociation-informed interventions.

Psychoform and somatoform dissociation in anorexia nervosa: A systematic review.

Dissociation is a debilitating condition often present as comorbidity in patients with eating disorders, but to date only sparse findings are available on this topic. Additionally, very little data exist on the classification of dissociation, namely, psychoform and somatoform, in anorexia nervosa (AN). This review aimed to provide an updated view on the literature about dissociation in AN, with a focus on AN subtypes (i.e., restricter and binge-purging) as well as dissociation type (i.e., psychoform and somatoform), when available. We screened 304 studies, and after title and abstract selection and full-text reading, 29 of them were included in this review. Most of the studies investigated psychoform dissociation, whereas just four publications considered somatoform dissociation. Dissociation resulted to be present in AN more than in healthy controls and in individuals with other psychiatric disorders, and it was related mostly to the binge-purging subtype of AN. Moreover, dissociation was linked to traumatic events, self-harm and negative treatment outcomes, especially in patients affected by the binge-purging subtype of AN. However, results on these matters are scarce and partially discordant. The methodological assessment we performed revealed an overall fair quality of the included studies, although several flaws emerged as well. The present review reported on one hand the relevance of dissociation in AN, but on the other hand the need to stimulate the scientific debate on (a) a deeper investigation of somatoform dissociation in AN and (b) the relationship between dissociation and both clinical severity and treatment response/resistance in AN.

The role of prenatal and perinatal factors in eating disorders: a systematic review.

Numerous studies showed that factors influencing fetal development and neonatal period could lead to lasting alterations in the brain of the offspring, in turn increasing the risk for eating disorders (EDs). This work aims to systematically and critically review the literature on the association of prenatal and perinatal factors with the onset of EDs in the offspring, updating previous findings and focusing on anorexia nervosa (AN) and bulimia nervosa (BN). A systematic literature search was performed on Pubmed, PsycINFO, and Scopus. The drafting of this systematic review was conducted following the PRISMA statement criteria and the methodological quality of each study was assessed by the MMAT 2018. A total of 37 studies were included in this review. The factors that showed a more robust association with AN were higher maternal age, preeclampsia and eclampsia, multiparity, hypoxic complications, prematurity, or being born preterm (< 32 weeks) and small for gestational age or lower birth size. BN was only associated with maternal stress during pregnancy. Many methodological flaws emerged in the considered studies, so further research is needed to clarify these inconsistencies. Altogether, data are suggestive of an association between prenatal and perinatal factors and the onset of EDs in the offspring. Nevertheless, given the methodological quality of the available literature, firm conclusions cannot be drawn and whether this vulnerability is specific to EDs or mental disorders remains to be defined. Also, a strong need for longitudinal and well-designed studies on this topic emerged.

Discovery and optimization of pyrazole amides as antagonists of CCR1.

A HTS screen for CCR1 antagonists afforded a novel sub-micromolar hit 5 containing a pyrazole core. In this report the design, optimization, and SAR of novel CCR1 antagonists based on a pyrazole core motif is presented. Optimization led to the advanced candidate compounds (S)-16q and (S)-16r with 250-fold improved CCR1 potency, excellent off-target selectivity and attractive drug-like properties.

Selective targeting of the IL23 pathway: Generation and characterization of a novel high-affinity humanized anti-IL23A antibody.

Herein, we describe the generation and characterization of BI 655066, a novel, highly potent neutralizing anti-interleukin-23 (IL23) monoclonal antibody in clinical development for autoimmune conditions, including psoriasis and Crohn's disease. IL23 is a key driver of the differentiation, maintenance, and activity of a number of immune cell subsets, including T helper 17 (Th17) cells, which are believed to mediate the pathogenesis of several immune-mediated disorders. Thus, IL23 neutralization is an attractive therapeutic approach. Designing an antibody for clinical activity and convenience for the patient requires certain properties, such as high affinity, specificity, and solubility. These properties were achieved by directed design of the immunization, lead identification, and humanization procedures. Favorable substance and pharmacokinetic properties were established by biophysical assessments and studies in cynomolgus monkeys.

Slow versus standard up-titration of paroxetine for the treatment of depression in cancer patients: a pilot study.

OBJECTIVES: This study aimed to compare the tolerability and efficacy of two different titrations of paroxetine (slow and standard) in a population of cancer patients with depression. METHODS: This randomized open trial included 30 cancer patients with depression (major depressive disorder, dysthymic disorder, or adjustment disorder with depressed mood) and aimed to compare the safety of slow up-titration (arm A) versus standard up-titration (arm B) of paroxetine chlorhydrate. In both arms, the maximum final dose was 20 mg/day. Patients were evaluated at baseline and after 2, 4, and 8 weeks with rating scales for depression and anxiety (MADRS, HADS, HAM-A, CGI), quality of life (EORTC-QLQ-30), and side effects (DOTES, SIDE). RESULTS: Thirty consecutive cancer patients (F = 21; M = 9) meeting DSM-IV TR criteria for mood disorders (MD) were enrolled in the study and randomly assigned to slow or standard paroxetine titration. Both treatment groups showed a significant mood improvement (change in MADRS total score) from baseline to end point (arm A-F(2,18) = 33.68 p < 0.001; arm B-F(2,12) = 6.97 p < 0.005). A significantly higher rate of patients in arm A compared with arm B showed no side effects after 2 weeks (40% vs. 6.7%, respectively). A multinomial logistic regression confirmed such differences between arms (chi square = 20.89 p = 0.004). The self-evaluating scale (SIDE) confirmed this difference: 60% of subjects in arm B perceived side effects compared to only 11.1% of patients in arm A. CONCLUSIONS: The results of this study suggest that slow paroxetine up-titration is better tolerated and at least as effective as the standard paroxetine up-titration in cancer patients with depression.

SAR studies of non-zinc-chelating MMP-13 inhibitors: improving selectivity and metabolic stability.

SAR studies to improve the selectivity and metabolic stability of a class of recently discovered MMP-13 inhibitors are reported. Improved selectivity was achieved by modifying interactions with the S1' pocket. Metabolic stability was improved through reduction of inhibitor lipophilicity. This translated into lower in vivo clearance for the preferred compound.

Sequence variation in group A Streptococcus pili and association of pilus backbone types with lancefield T serotypes.

BACKGROUND: We previously reported that group A Streptococcus (GAS) pili are the T antigens described by Rebecca Lancefield. We also showed that these pili, constituted by backbone, ancillary 1, and ancillary 2 proteins, confer protection against GAS challenge in a mouse model. METHODS: We evaluated pilus distribution and conservation by sequencing the subunits of 39 new GAS isolates and used immunoblot analysis and agglutination assays to define the specificity of T sera to pilus subunits. RESULTS: GAS pili are encoded by 9 different islands within which backbone protein, ancillary protein 1, and ancillary protein 2 cluster in 15, 16, and 5 variants, respectively. Immunoblot and agglutination assays revealed that T type is determined by the backbone variant. This observation enabled us to set up a simple polymerase chain reaction assay to define the T type of GAS isolates. CONCLUSIONS: We propose the use of a tee gene sequence typing, analogous to the emm gene typing, as a valuable molecular tool that could substitute for the serological T classification of GAS strains. From our sequence analysis and from recent epidemiological data, we estimate that a vaccine comprising a combination of 12 backbone variants would protect against > 90% of currently circulating strains.