Eating disorders, bipolar disorders and other mood disorders : complex and under-researched relationships

Eating disorders are understood to no longer be the remit of lean adolescent girls alone [1], whatever pop culture offerings such as Netflix’s To The Bone might continue to present. Rather, people with eating disorders are much more diverse, often undiagnosed and often suffering in silence. One patient population with a unique but poorly understood vulnerability to eating disorders, as well as obesity and poor physical health, is people with bipolar disorder

A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo

A phasic dysregulation of mitochondrial bioenergetics may operate in bipolar disorder, increased in mania and decreased in depression. We aimed to examine efficacy of two add-on treatments in bipolar depression: N-acetylcysteine (NAC) and NAC with a combination of nutraceutical agents that may increase mitochondrial biogenesis. A three-arm 16-week, double-blind, randomised, placebo-controlled trial, adjunctive to usual treatment, was conducted. Participants (n = 181) with bipolar disorder and current depressive symptoms were randomised to 2000 mg/day NAC (n = 59), 2000 mg/day NAC with the combination nutraceutical treatment (CT, n = 61), or placebo (n = 61). The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 16. Young Mania Rating Scale, Clinical Global Impression (CGI)-Improvement and CGI-Severity scales, Patient Global Impression scale, Social and Occupational Functioning Assessment Scale (SOFAS), Longitudinal Interval Follow-Up Evaluation - Range of Impaired Functioning Tool (LIFE-RIFT), and Quality of Life Enjoyment, and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) were secondary outcomes. One hundred forty-eight participants had post-randomisation data and were analysed (NAC = 52, CT = 47, Placebo = 49). No between-group differences were found for the rate of change between baseline and 16 weeks on any of the clinical and functioning variables. Improvements in MADRS, BDRS, SOFAS, and LIFE-RIFT scores from baseline to the week 20 post-discontinuation visit were significantly greater in the CT group compared to those in the placebo. At week 20, the CGI-I was significantly lower in the CT group versus placebo. Gastrointestinal symptoms were significantly greater in the NAC than in the placebo group. These overall negative results, with no significant differences between groups detected at the primary outcome but some positive secondary signals, suggest either delayed benefit of the combination or an improvement of symptoms on withdrawal which warrants further exploration regarding the composition, mechanisms, and application of mitochondrial agents in illnesses characterised by mitochondrial dysfunction. ANZCTR ( ACTRN12612000830897 )

HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for: 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL=1.31, 95% CI=1.06-1.60; OR MZL=1.45, 95% CI=1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL=2.10, 95% CI=1.24-3.55; OR MZL= 2.10, 95% CI=0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (p-trend<0.0001, FDR=0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Eating Disorder Features in Bipolar Disorder: Course, Psychological Correlates, and Relationship with Quality of Life

Despite growing interest in eating disorders (EDs) comorbid with bipolar disorder (BD), little research has considered the nature of ED features and their association with physical health and psychosocial outcomes. The current research aimed to assess ED features in people with BD and their association with BMI and psychological factors. People with BD (Aus=73, Netherlands=109) completed online questionnaires and 9 Australian participants with the comorbidity participated in a qualitative interview. In total, 31 (19%) were identified as having a probable ED, most commonly binge eating disorder (45%). Only one reported a formally-diagnosed ED. Comorbid EDs were associated with significantly poorer emotion regulation ability, reduced quality of life (QoL), and higher distress, but not impulsivity. Greater depressive symptoms and more frequent hospital admissions for depression were also reported. The most common ED features were weight/shape overvaluation (36%) and objective binge eating episodes (OBEs; 21%). OBEs and restriction uniquely contributed to poorer QoL in a regression model. Positive beliefs about the function of binge eating, but not OBEs, predicted higher body mass index (BMI). Interviews revealed that BD illness episodes often correlated with changes in eating and BMI. Most participants connected their experience of an ED and BD to traumatic experiences. None felt that concerns with their eating, weight gain and physical health had been adequately addressed. Results suggest that this double diagnosis and even subthreshold EDs in BD are associated with elevated ED cognitions and heightened difficulties with emotion regulation. Clinicians and researchers alike should consider more proactive screening for this comorbidity as a significant contributing factor to disability. Future interventions for this under-supported group could consider targeting cognitive processes, emotion regulation difficulties and comorbid traumatic stress disorders

Early intervention for bipolar disorder in adolescents : a psychosocial perspective

Aim: Early intervention in bipolar disorder (BD) has received increasing attention in recent years. The identification of risk factors has improved, but researchers continue to struggle to find an effective treatment once the illness has become established. The aetiology of BD and feasibility of early intervention present a challenge, making it difficult to decide who to target, as well as how. Methods: This essay seeks to address the lack of guidance for managing patients with a possible emerging bipolar illness, by presenting a rough roadmap to psychological care. The psychological techniques currently showing the most potential for this challenging group are reviewed. Markers of risk and supplementary clinical targets, such as anxiety and sleep disruption, are also discussed. Results: While research in this group remains in its infancy, various avenues of enquiry show promise, such as family-based approaches, CBT that targets features beyond the core illness, psychoeducation, and interventions that consider physical health. However, clearer pathways for establishing the course and stage of the illness are required to inform the intensity and type of treatment. Conclusion: It is argued that treating early, indistinct symptoms of psychological distress, that may or may not signify prodromal BD, is valuable beyond its utility as an early intervention tool, as it has the capacity to improve help-seeking behaviour, quality of life and the likelihood of functional recovery in those who go on to develop the illness as adults

"The food matches the mood" : experiences of eating disorders in bipolar disorder

Approximately 33% of those with bipolar disorder (BD) have a comorbid eating disorder (ED). However, the trajectory of these conditions has received little research attention. Nine participants who met criteria for BD and an ED participated in qualitative interviews exploring experiences of illness onset, the interaction of these conditions, and service provision. Almost all participants in the sample reported minimal to no screening of ED problems, despite their health professionals’ frequent discussion of obesity. Findings suggested that ED features were diverse and evolved over time. Mania and depression were connected to ED features such as overeating and restricting, but this differed between and within participants. Most participants disclosed historic trauma which they considered central to their mental health concerns. This clinical group appears to be underserviced. Clinicians and researchers should routinely screen for ED features when treating and diagnosing BD to inform their physical and mental health interventions

High or low intensity text-messaging combined with group treatment equally promote weight loss maintenance in obese adults

BACKGROUND Text-message and e-mail are emerging as potential methods for improving weight outcomes among obese individuals. The optimal volume, frequency, and timing of such interventions are unknown. This study investigated the effect of adjunct technological support on weight and psychological variables after a 3-month cognitive-behaviour therapy (CBT) group intervention. METHODS Sixty obese adults were randomised to a CBT programme plus intensive (text-message and e-mail; CBT+ITS) or minimal (text-message only; CBT+MTS) technological support. Assessments occurred at baseline, 3-, 6-, 9-, and 15-months. Outcome variables included weight (kg), body mass index (kg/m(2)), waist circumference (cm), binge-eating tendencies, weight self-efficacy, and weight control cognitions and behaviours. RESULTS CBT+ITS (n=31) and CBT+MTS (n=29) participants lost 5.2% (±1.1) and 4.7% (±1.1) of their baseline weight by 3-months, 8.4% (±1.2) and 6.4% (±1.1) by 6-months, 9.6% (±1.3) and 6.4% (±1.3) by 9-months, and sustained a 7.5% (±1.3) and 5.1% (±1.3) loss at 15-months, respectively. There were no significant differences between intensive and minimal support, however, the CBT+ITS group showed a marginal advantage across all anthropometric measures. CONCLUSIONS A low intensity text-message support programme is just as effective as higher intensity technological support for maintaining weight loss in obese adults. This represents a low-cost means of aiding weight loss maintenance without reliance on extended face-to-face treatment

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification. Funding UK Research and Innovation and National Institute for Health Research

Confounding Factors in Targeted Degradation of Short-Lived Proteins

Targeted protein degradation has recently emerged as a novel option in drug discovery. Natural protein half-life is expected to affect the efficacy of degrading agents, but to what extent it influences target protein degradation has not been systematically explored. Using simple mathematical modeling of protein degradation, we find that the natural half-life of a target protein has a dramatic effect on the level of protein degradation induced by a degrader agent which can pose significant hurdles to screening efforts. Moreover, we show that upon screening for degraders of short-lived proteins, agents that stall protein synthesis, such as GSPT1 degraders and generally cytotoxic compounds, deceptively appear as protein-degrading agents. This is exemplified by the disappearance of short-lived proteins such as MCL1 and MDM2 upon GSPT1 degradation and upon treatment with cytotoxic agents such as doxorubicin. These findings have implications for target selection as well as for the type of control experiments required to conclude that a novel agent works as a bona fide targeted protein degrader.</p