The epidemiological and clinical characteristics of patients with young-onset genetic Creutzfeldt-Jakob disease.

OBJECTIVES: The onset of Creutzfeldt-Jakob disease (CJD) is usually around the age of 60, but younger patients have been described as well. Our study characterizes the demographic and clinical features of young-onset CJD patients. METHODS: The CJD Israeli National Database was reviewed, and the patients were divided into groups of young (<40-year-old) (Y|) and older disease onset (>40-year-old) (O). Each group was further divided into sporadic (sCJD) and genetic (gCJD) patients. Clinical and demographic parameters were compared between the groups. RESULTS: The study included 731 patients (Y- 18 patients, O- 713 patients). MRI showed classical features more often in the older population (O-76.9%, Y-36%, p = 0.006). Rapidly progressive dementia as a presenting feature was more common in the older group (O = 58%, Y = 27.7%, p = 0.019) whereas cerebellar onset (gait instability, dysarthria) was more common in the younger group (O = 6.7%, Y = 27.7%, p = 0.036)). Among gCJD patients, rapidly progressive dementia was commonly seen in older patients (O = 54%, Y = 21% p = 0.008) whereas cerebellar symptoms were seen in young patients (O = 7%, Y = 30% p = 0.01) Typical MRI findings were seen in 37% of young people compared to 87% of older patients (p = 0.002). No significant differences were between young and older patients in the sCJD group. CONCLUSION: Young-onset gCJD patients have unique disease features including less typical brain MRI changes, a lower prevalence of dementia, and a higher prevalence of cerebellar signs at disease onset.

Plasma levels of one-carbon metabolism nutrients in women with anorexia nervosa.

OBJECTIVE: People who are ill with anorexia nervosa (AN) show altered availability of key plasma nutrients. However, little is known about the patterning of alterations that occurs across diverse nutrients during active phases of illness or about the persistence of any such alterations following remission of illness. METHOD: We compared plasma levels of one-carbon metabolism nutrients across women with active AN (AN-Active: n = 53), in remission from AN (AN-Remitted: n = 40), or who had no eating-disorder history (NED: n = 36). We also tested associations between body mass index (BMI) changes and changes in pre- to posttreatment nutrient levels, and explored the association between nutrient levels, on the one hand, and BMI and eating symptoms, on the other. Choline, betaine, and methionine were analyzed using mass spectrometry. Folate and B12 were analyzed using the AccuBind® ELISA kit. Eating-disorder symptoms were assessed by interview and self-report. RESULTS: Compared to NED individuals, AN-Active individuals exhibited significantly elevated B12 and (less-reliably) betaine. In AN-Active individuals, lower BMI was associated with higher B12. DISCUSSION: The observed alterations run contrary to the intuition that plasma nutrient levels should be directly responsive to nutritional status and suggest, instead, the existence of compensatory adaptations to malnutrition in individuals with active AN. Further study is required to clarify mechanisms that underlie such effects.

Methylation of the OXTR gene in women with anorexia nervosa: Relationship to social behavior.

DNA methylation allows for the environmental regulation of gene expression and is believed to link environmental stressors to psychiatric disorder phenotypes, such as anorexia nervosa (AN). The oxytocin receptor (OXTR) gene is epigenetically regulated, and studies have shown associations between OXTR and social behaviours in various samples, including women with AN. The present study examined differential levels of methylation at various CG sites of the OXTR gene in 69 women with active AN (AN-Active), 21 in whom AN was in remission (AN-Rem) and 35 with no eating disorder (NED). Within each group, we explored the correlation between methylation and measures of social behaviour such as insecure attachment and social avoidance. Hypermethylation of a number of CG sites was seen in AN-Active participants as compared with AN-Rem and NED participants. In the AN-Rem sample, methylation at CG27501759 was significantly positively correlated with insecure attachment (r = .614, p = .003, permutation Q = 0.008) and social avoidance (r = .588, p = .005, permutation Q = 0.0184). Our results highlight differential methylation of the OXTR gene among women with AN, those in remission from AN, and those who never had AN and provide some evidence of associations between OXTR methylation and social behaviour in women remitted from AN.

A naturalistic comparison of two inpatient treatment protocols for adults with anorexia nervosa: Does reducing duration of treatment and external controls compromise outcome?

OBJECTIVE: Although hospitalization is sometimes necessary when treating individuals with anorexia nervosa, the available literature provides limited guidance to inform decisions surrounding optimal components or duration of inpatient treatments. We report observational data comparing outcomes of two inpatient treatments. The first was longer and more strictly structured around a Contingency Management Protocol (CMP) emphasizing external incentives for achieving weight-restoration goals; the second was a shorter Autonomy Support Protocol (ASP) that progressively increased patient autonomy around meal management without external incentives. METHOD: We compared data from 41 patients who participated in the ASP to a historical sample of 41 patients treated using the CMP. At admission, discharge, and post-treatment follow-up, participants completed the Eating Disorder Examination Questionnaire and the Behavior and Symptom Identification Scale-32, and we measured height and weight to compute body mass index. RESULTS: Multilevel modeling analyses that controlled for time in treatment and time in follow-up indicated the two protocols yielded equivalent in-treatment gains and post-treatment loss of gains. DISCUSSION: Our results indicate that shorter inpatient stays emphasizing autonomous control over eating behavior may yield outcomes that are equivalent to those of lengthier, more stringent, and more costly approaches implicating external incentives and controls.

A longitudinal, epigenome-wide study of DNA methylation in anorexia nervosa: results in actively ill, partially weight-restored, long-term remitted and non-eating-disordered women

Background: This study explored state-related tendencies in DNA methylation in people with anorexia nervosa. Methods: We measured genome-wide DNA methylation in 75 women with active anorexia nervosa (active), 31 women showing stable remission of anorexia nervosa (remitted) and 41 women with no eating disorder (NED). We also obtained post-intervention methylation data from 52 of the women from the active group. Results: Comparisons between members of the active and NED groups showed 58 differentially methylated sites (Q < 0.01) that corresponded to genes relevant to metabolic and nutritional status (lipid and glucose metabolism), psychiatric status (serotonin receptor activity) and immune function. Methylation levels in members of the remitted group differed from those in the active group on 265 probes that also involved sites associated with genes for serotonin and insulin activity, glucose metabolism and immunity. Intriguingly, the direction of methylation effects in remitted participants tended to be opposite to those seen in active participants. The chronicity of Illness correlated (usually inversely, at Q < 0.01) with methylation levels at 64 sites that mapped onto genes regulating glutamate and serotonin activity, insulin function and epigenetic age. In contrast, body mass index increases coincided (at Q < 0.05) with generally increased methylation-level changes at 73 probes associated with lipid and glucose metabolism, immune and inflammatory processes, and olfaction. Limitations: Sample sizes were modest for this type of inquiry, and findings may have been subject to uncontrolled effects of medication and substance use. Conclusion: Findings point to the possibility of reversible epigenetic alterations in anorexia nervosa, and suggest that an adequate pathophysiological model would likely need to include psychiatric, metabolic and immune components.

Prognostic value of autonomous and controlled motivation in outpatient eating-disorder treatment.

According to Self-Determination Theory, when motivation to reach an objective is fully internal, it is said to be "autonomous"; when driven by external incentives, it is said to be "controlled". Previous research has indicated that autonomously motivated individuals show better response to treatments for eating disorders. OBJECTIVE: In individuals undergoing different intensities of outpatient treatment for an eating disorder, we sought to assess associations between autonomous and controlled motivations and response to treatment on the one hand, and likelihood of dropping out of treatment, on the other. METHOD: Seven hundred seventy adults meeting DSM-5 criteria for an eating disorder (216 with Anorexia Nervosa, 282 with Bulimia Nervosa, and 272 with Other Specified Feeding or Eating Disorder) were included in this study. Before an interval of outpatient treatment, individuals completed the Eating Disorder Examination Questionnaire and the Autonomous and Controlled Motivations for Treatment Questionnaire. Participants completed the Eating Disorder Examination Questionnaire again at one or two subsequent timepoints. RESULTS: After controlling for diagnosis, treatment intensity, and number of previous treatments, analyses showed that higher autonomous motivation was associated with better response on eating-disorder overall symptoms and lower likelihood of dropping out of treatment. In contrast, controlled motivation was not associated with response to treatment. DISCUSSION: Our results suggest that autonomous motivation has trans-diagnostic influence upon response to various intensities of treatment for an eating disorder. In support of an autonomy supportive approach to treatment, findings link autonomous motivation with more favorable outcome.

Correction to: A Tertiary-Care/Primary-Care Partnership Aimed at Improving Care for People with Eating Disorders.

The original version of this article unfortunately contained a mistake in EAT-26 values under "Patients Receiving Treatment for an ED in their Sector" section.

A Tertiary-Care/Primary-Care Partnership Aimed at Improving Care for People with Eating Disorders.

We describe the implementation and impact of a province-wide program of knowledge exchange (KE), aimed at developing capacity for the treatment of people with eating disorders (EDs). The program is designed to equip clinicians working in nonspecialized health-care installations with skills to evaluate and treat people with EDs. Trainings were conducted at 21 institutions. The majority of clinicians reported satisfaction with the KE program and indicated that the trainings enhanced their confidence and ability to treat patients with EDs. A subset of clinicians received case supervision with a specialist ED therapist and followed patients with EDs (n = 119). Treated patients showed significant improvements on eating and depressive symptoms, and reported satisfaction with the treatments they received.

Autonomy support and autonomous motivation in the outpatient treatment of adults with an eating disorder.

OBJECTIVE: Across diverse clinical problems, therapists' autonomy support has been found to increase patients' autonomous motivation for change. Being self-motivated has, in turn, been linked to superior treatment response. In people undergoing outpatient eating disorder (ED) treatment, we examined associations among ratings of autonomy support received from therapists and other carers, self-reported engagement in therapy, and clinical outcomes. METHOD: Ninety-seven women with anorexia nervosa, bulimia nervosa, or a related ED provided measures of motivational status and clinical symptoms at the beginning and end of time-limited (12-16 weeks) segments of specialized treatment. At mid-treatment, patients also rated the extent to which they perceived their individual therapists, group therapists, group-therapy peers, family members, friends, and romantic partners as being autonomy supportive. RESULTS: Overall, multiple regression analyses indicated autonomy support to moderate (rather than mediate) the link between initial autonomous motivation and later change in autonomous motivation-with results indicating that, independently of ED diagnosis or treatment intensity, greater perceived autonomy support (from therapists and nontherapists alike) coincided with larger increases in autonomous motivation over the course of therapy. In turn, higher autonomous motivation at end-of-therapy coincided with larger reductions in eating symptoms. DISCUSSION: Findings suggest that the experience of autonomy support (from therapists and nontherapists) is associated with increasing motivation in people undergoing ED treatment, and that becoming self-motivated is linked to better outcomes. Such results indicate that support from therapists, relatives, and peers can favorably influence personal engagement in individuals undergoing ED treatment.