The impact of genetic risk for schizophrenia on eating disorder clinical presentations.

A growing body of literature recognizes associations between eating disorders (EDs) and schizophrenia and suggests that familial liability to schizophrenia in individuals with anorexia nervosa (AN) reveals distinct patterns of clinical outcomes. To further investigate the influence of schizophrenia genetic liability among individuals with EDs, we evaluated the associations between schizophrenia polygenic risk scores (PRS) and clinical presentations of individuals with EDs including their overall health condition and ED-related symptoms. Using data from two previous studies of the genetics of EDs comprising 3,573 Anorexia Nervosa Genetics Initiative (ANGI) cases and 696 Binge Eating Genetics Initiative (BEGIN) cases born after 1973 and linked to the Swedish National Patient Register, we examined the association of schizophrenia PRS on ED clinical features, psychiatric comorbidities, and somatic and mental health burden. Among ANGI cases, higher schizophrenia PRS was statistically significantly associated with higher risk of major depressive disorder (MDD) measured by hazard ratio (HR) with 95% confidence interval (CI) (HR [95% CI]: 1.07 [1.02, 1.13]) and substance abuse disorder (SUD) (HR [95% CI]: 1.14 [1.03, 1.25]) after applying multiple testing correction. Additionally, higher schizophrenia PRS was associated with decreased clinical impairment assessment scores (-0.56, 95% CI: [-1.04, -0.08]) at the conventional significance level (p < 0.05). Further, in BEGIN cases, higher schizophrenia PRS was statistically significantly associated with earlier age at first ED symptom (-0.35 year, 95% CI: [-0.64, -0.06]), higher ED symptom scores (0.16, 95% CI: [0.04, 0.29]), higher risk of MDD (HR [95% CI]: 1.18 [1.04, 1.34]) and SUD (HR [95% CI]: 1.36 [1.07, 1.73]). Similar, but attenuated, patterns held in the subgroup of exclusively AN vs other eating disorder (OED) cases. These results suggest a similar pattern of influence of schizophrenia PRS for AN and OED cases in terms of psychiatric comorbidities, but a different pattern in terms of ED-related clinical features. The disparity of the effect of schizophrenia PRS on AN vs OED merits further investigation.

Proposal for increasing diagnostic clarity in research and clinical practice by renaming and reframing atypical anorexia nervosa as "Restrictive Eating Disorder" (RED).

Atypical anorexia nervosa (AAN) in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), is characterized by meeting all criteria for anorexia nervosa (AN) except for weight being within or above the "normal" range despite significant weight loss. The current definition is plagued by several problems, resulting in widely heterogeneous operationalizations in research and clinical practice. As such, the poorly defined diagnosis of AAN negatively impacts affected individuals and frustrates research attempts to better understand the syndrome. We consider conceptual flaws in the AAN description and contend that the undefined weight range and nature of weight loss renders these two factors functionally inapplicable in research and practice. They also represent a departure from the originally intended use of the AAN category, i.e., arresting a negative weight trajectory likely to result in AN, making the target population, and the application of the label, unclear. We propose revised criteria and a new name, restrictive eating disorder (RED), intended to reduce stigma and encompass a wide but better-defined range of presentations. The RED criteria focus on clinically significant restrictive behavior that disrupts normal living (i.e., impairment), and cognitive symptoms of overevaluation, disturbed experience, and lack of recognition of illness seriousness. We believe that RED may enable more appropriate clinical application, but also inspire coordinated research toward a more valid psychiatric nosology in the eating disorders field.

Course and predictors of eating disorder symptoms, anxiety symptoms, and pandemic-related eating disorder concerns among adults with eating disorders during the first year of the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic and public health mitigation measures have negatively impacted individuals with eating disorders (ED). We evaluated changes in and predictors of ED symptoms, pandemic-related ED concerns, and anxiety symptoms across the first 12 months of the COVID-19 pandemic among individuals with self-reported EDs in the United States (US), Sweden (SE), and the Netherlands (NL). METHOD: Participants in the US (N = 510), SE (N = 982), and NL (N = 510) completed an online survey assessing ED symptoms (binge eating, restriction, compensatory behaviors, and anxiety about being unable to exercise), general anxiety symptoms, and pandemic-related ED concerns about accessing food, lack of structure and social support, being in a triggering environment, and food and treatment costs. In the US and NL, respondents completed surveys beginning April 2020 and continuing monthly for a year. In SE, respondents completed baseline surveys in May 2020, a six-month follow-up around December 2020, and a 12-month follow-up in May 2021. RESULTS: Three patterns emerged: (1) a curvilinear course with the highest level of symptoms at baseline, declining through November 2020, and increasing through the rest of the year; (2) a linear declining course over time; and (3) a stable course with no changes. Worries about COVID-19 infection, lockdown, concerns about lack of structure and social support, and concerns about accessing food consistent with one's recovery meal plan predicted increases in ED symptoms. DISCUSSION: ED symptoms tracked with pandemic-related concerns in people with EDs. Conceptualizing predictors of symptoms may inform therapy and public health resources that reduce the impact of pandemics on mental health. PUBLIC SIGNIFICANCE: Our findings suggest that the COVID-19 pandemic had negative impacts on people with eating disorders, including amplification of mental health symptoms and stressors around peak periods of infection and COVID-19 restrictions. These findings inform medical providers, policy-makers, and community-based supports about the information and resource needs of this group to ensure efficient dissemination in future public health emergencies and during the ongoing COVID-19 pandemic.

Longer-term impact of COVID-19 among individuals with self-reported eating disorders in the United States, the Netherlands, and Sweden.

OBJECTIVE: We assessed eating disorder (ED) illness status, symptomatology, treatment access, anxiety, and depression in the first year of the COVID-19 pandemic among individuals with a pre-existing ED in the United States (US), the Netherlands (NL), and Sweden (SE). METHODS: Participants completed online surveys in April-July 2020, at the early stage of the pandemic, and one year later. At one-year follow-up, we added questions addressing retrospective changes in ED symptoms, treatment, and anxiety/depression since the start of the COVID-19 pandemic. We present descriptive statistics and assess change in ED symptomatology, treatment, and anxiety/depression among those with an active or lingering ED. RESULTS: Participants (US n = 132; NL n = 219; SE n = 702) were mostly young and female with a history of anorexia nervosa (>60% in all three countries). Across countries, respondents reported impact of COVID-19 on ED symptoms at both time points, with improvement in US and NL at one-year follow-up, and stable but less impact on ED symptoms in SE. Furthermore, at one-year follow-up, roughly half of those in treatment reported reduced treatment access and quality, and the majority of the sample reported increased anxiety and depressive mood since the start of the pandemic. DISCUSSION: Our findings suggest that the self-perceived impact of COVID-19 changed over time but remained concerning even one year after the start of the pandemic. Clinicians, community organizations, and policy makers are encouraged to address potentially changing treatment needs in the face of public health emergency events. PUBLIC SIGNIFICANCE: Our findings suggest that the impact of COVID-19 on individuals with eating disorders decreased over time but remained concerning even one year after the start of the pandemic and that the impact differed across countries. Clinicians, community organizations, and policy makers are encouraged to incorporate this knowledge to address potentially changing treatment needs in the face of public health emergency events.

Longitudinal experiences and impact of the COVID-19 pandemic among people with past or current eating disorders in Sweden.

The study aimed to document the impact of the COVID-19 pandemic on the health and well-being of individuals with past and current eating disorders (ED) in Sweden. We re-contacted participants with a known lifetime history of ED from two previous Swedish studies. Participants completed an online survey about health and functioning at baseline early in the pandemic (Wave 1 ca May/June 2020; N= 982) and six months later (Wave 2 Dec/Jan 2020/21; N= 646). Three important patterns emerged: 1) higher current ED symptoms were associated with greater anxiety, worry, and pandemic-related ED symptom increase; 2) patterns were fairly stable across time, although a concerning percentage (23%) who were symptom-free at Wave 1 reported the re-emergence of symptoms at Wave 2; and 3) only a minority of participants (<50%) with a current ED were in treatment, and of those in treatment, many reported fewer treatment sessions and decreased quality of care. The COVID-19 pandemic appears to pose serious health challenges for individuals with an ED, whether currently symptomatic or in remission. We encourage health service providers and patient advocates to be alert to the needs of individuals with ED and to take active measures to ensure access to appropriate evidence-based care both during and following the pandemic.

Resin-acid derivatives bind to multiple sites on the voltage-sensor domain of the Shaker potassium channel.

Voltage-gated potassium (KV) channels can be opened by negatively charged resin acids and their derivatives. These resin acids have been proposed to attract the positively charged voltage-sensor helix (S4) toward the extracellular side of the membrane by binding to a pocket located between the lipid-facing extracellular ends of the transmembrane segments S3 and S4. By contrast to this proposed mechanism, neutralization of the top gating charge of the Shaker KV channel increased resin-acid-induced opening, suggesting other mechanisms and sites of action. Here, we explore the binding of two resin-acid derivatives, Wu50 and Wu161, to the activated/open state of the Shaker KV channel by a combination of in silico docking, molecular dynamics simulations, and electrophysiology of mutated channels. We identified three potential resin-acid-binding sites around S4: (1) the S3/S4 site previously suggested, in which positively charged residues introduced at the top of S4 are critical to keep the compound bound, (2) a site in the cleft between S4 and the pore domain (S4/pore site), in which a tryptophan at the top of S6 and the top gating charge of S4 keeps the compound bound, and (3) a site located on the extracellular side of the voltage-sensor domain, in a cleft formed by S1-S4 (the top-VSD site). The multiple binding sites around S4 and the anticipated helical-screw motion of the helix during activation make the effect of resin-acid derivatives on channel function intricate. The propensity of a specific resin acid to activate and open a voltage-gated channel likely depends on its exact binding dynamics and the types of interactions it can form with the protein in a state-specific manner.

Early impact of COVID-19 on individuals with self-reported eating disorders: A survey of ~1,000 individuals in the United States and the Netherlands.

OBJECTIVE: We evaluated the early impact of COVID-19 on people with self-reported eating disorders. METHOD: Participants in the United States (US, N = 511) and the Netherlands (NL, N = 510), recruited through ongoing studies and social media, completed an online survey that included both quantitative measures and free-text responses assessing the impact of COVID-19 on situational circumstances, eating disorder symptoms, eating disorder treatment, and general well-being. RESULTS: Results revealed strong and wide-ranging effects on eating disorder concerns and illness behaviors that were consistent with eating disorder type. Participants with anorexia nervosa (US 62% of sample; NL 69%) reported increased restriction and fears about being able to find foods consistent with their meal plan. Individuals with bulimia nervosa and binge-eating disorder (US 30% of sample; NL 15%) reported increases in their binge-eating episodes and urges to binge. Respondents noted marked increases in anxiety since 2019 and reported greater concerns about the impact of COVID-19 on their mental health than physical health. Although many participants acknowledged and appreciated the transition to telehealth, limitations of this treatment modality for this population were raised. Individuals with past histories of eating disorders noted concerns about relapse related to COVID-19 circumstances. Encouragingly, respondents also noted positive effects including greater connection with family, more time for self-care, and motivation to recover. DISCUSSIONS: COVID-19 is associated with increased anxiety and poses specific disorder-related challenges for individuals with eating disorders that require attention by healthcare professionals and carers.

Early Impact of COVID-19 on Individuals with Eating Disorders: A survey of ~1000 Individuals in the United States and the Netherlands.

We received rapid ethical permission to evaluate the early impact of COVID-19 on people with eating disorders. Participants in the United States (US, N=511) and the Netherlands (NL, N=510), recruited through ongoing studies and social media, completed an online baseline survey that included both quantitative measures and free-text responses assessing the impact of COVID-19 on situational circumstances, eating disorder symptoms, eating disorder treatment, and general well-being. Results revealed strong and wide-ranging effects on eating disorder concerns and illness behaviors that were consistent with diagnoses. Participants with anorexia nervosa (US 62% of sample; NL 69%) reported increased restriction and fears about being able to find foods consistent with their meal plan. Individuals with bulimia nervosa and binge-eating disorder (US 30% of sample; NL 15%) reported increases in their binge-eating episodes and urges to binge. Respondents noted marked increases in anxiety since 2019 and reported greater concerns about the impact of COVID-19 on their mental health than physical health. Although many participants acknowledged and appreciated the transition to telehealth, limitations of this treatment modality for this population were raised. Individuals with past histories of eating disorders noted concerns about relapse related to COVID-19 circumstances. Encouragingly, respondents also noted positive effects including greater connection with family, more time for self-care, and motivation to recover.