Unraveling how the adolescent brain deals with criticism using dynamic causal modeling.

Sensitivity to criticism, which can be defined as a negative evaluation that a person receives from someone else, is considered a risk factor for the development of psychiatric disorders in adolescents. They may be more vulnerable to social evaluation than adults and exhibit more inadequate emotion regulation strategies such as rumination. The neural network involved in dealing with criticism in adolescents may serve as a biomarker for vulnerability to depression. However, the directions of the functional interactions between the brain regions within this neural network in adolescents are still unclear. In this study, 64 healthy adolescents (aged 14 to 17 years) were asked to listen to a series of self-referential auditory segments, which included negative (critical), positive (praising), and neutral conditions, during fMRI scanning. Dynamic Causal Modeling (DCM) with Parametric Empirical Bayesian (PEB) analysis was performed to map the interactions within the neural network that was engaged during the processing of these segments. Three regions were identified to form the interaction network: the left pregenual anterior cingulate cortex (pgACC), the left dorsolateral prefrontal cortex (DLPFC), and the right precuneus (preCUN). We quantified the modulatory effects of exposure to criticism and praise on the effective connectivity between these brain regions. Being criticized was found to significantly inhibit the effective connectivity from the preCUN to the DLPFC. Adolescents who scored high on the Perceived Criticism Measure (PCM) showed less inhibition of the preCUN-to-DLPFC connectivity when being criticized, which may indicate that they required more engagement of the Central Executive Network (which includes the DLPFC) to sufficiently disengage from negative self-referential processing. Furthermore, the inhibitory connectivity from the DLPFC to the pgACC was strengthened by exposure to praise as well as criticism, suggesting a recruitment of cognitive control over emotional responses when dealing with positive and negative evaluative feedback. Our novel findings contribute to a more profound understanding of how criticism affects the adolescent brain and can help to identify potential biomarkers for vulnerability to develop mood disorders before or during adulthood.

Detecting sparse microbial association signals adaptively from longitudinal microbiome data based on generalized estimating equations.

The association between the compositions of microbial communities and various host phenotypes is an important research topic. Microbiome association research addresses multiple domains, such as human disease and diet. Statistical methods for testing microbiome-phenotype associations have been studied recently to determine their ability to assess longitudinal microbiome data. However, existing methods fail to detect sparse association signals in longitudinal microbiome data. In this paper, we developed a novel method, namely aGEEMIHC, which is a data-driven adaptive microbiome higher criticism analysis based on generalized estimating equations to detect sparse microbial association signals from longitudinal microbiome data. aGEEMiHC adopts generalized estimating equations framework that fully considers the correlation among different observations from the same subject in longitudinal data. To be robust to diverse correlation structures for longitudinal data, aGEEMiHC integrates multiple microbiome higher criticism analyses based on generalized estimating equations with different working correlation structures. Extensive simulation experiments demonstrate that aGEEMiHC can control the type I error correctly and achieve superior performance according to a statistical power comparison. We also applied it to longitudinal microbiome data with various types of host phenotypes to demonstrate the stability of our method. aGEEMiHC is also utilized for real longitudinal microbiome data, and we found a significant association between the gut microbiome and Crohn's disease. In addition, our method ranks the significant factors associated with the host phenotype to provide potential biomarkers.

How can we further explore the link between self-criticism and self-compassion, and disordered eating? Commentary on Paranjothy and Wade's (2024).

Paranjothy and Wade's (2024, A meta-analysis of disordered eating and its association with self-criticism and self-compassion. International Journal of Eating Disorders. https://doi.org/10.1002/eat.24166) systematic review and meta-analysis of disordered eating and its association with self-criticism and self-compassion provides a valuable synthesis of 135 studies. They found that greater levels of self-criticism and increased disordered eating were associated with lower levels of self-compassion. These findings highlight the importance of further investigating the complex relationship between these variables to inform effective interventions. This commentary explores what the findings of Paranjothy and Wade (2024) tell us and how we can use their findings to address unresolved problems. I will focus on two primary areas in this commentary: (1) the specificity of self-criticism and (2) how we could use existing data to enhance the understanding of the etiology and maintenance of disordered eating in relation to self-criticism and self-compassion to conduct further research. This commentary argues that there is a need for refinement of the self-criticism construct (e.g., through qualitative research) to understand how self-criticism varies across different individuals and cultures, particularly for under-researched populations. I recommend further research using meta-analytic structural equation modeling to test different theoretical models to pin down how self-criticism and self-compassion function as mechanisms of change in disordered eating.

The ups and downs of self-criticism and disordered eating: Complementing Paranjothy and Wade's (2024) analysis by considering both trait and state perspectives.

Paranjothy and Wade's (2024) meta-review reveals that individuals higher in the personality trait of self-criticism consistently experience more disordered eating than those lower in the trait. The clinical implications of this meta-review are important in that they suggest current theoretical models and clinical practices in the field of eating disorders should incorporate a greater focus on self-criticism. Building on this exciting contribution, we highlight conceptual, practical, and empirical reasons why the field would benefit from supplementing this research on trait self-criticism with investigations of state self-criticism. We review research showing that self-criticism levels vary not only between individuals, with some people chronically more self-critical than others, but also within a person, with a given individual enacting relatively more self-criticism during some moments and days than others. We then present emerging research showing that these periods of higher-than-usual self-criticism are associated with more disordered eating. Thus, we emphasize the need to explore the factors that give rise to self-critical states in daily life, and review preliminary findings on this topic. We highlight the ways in which research on within-person variations in self-criticism can complement research on trait self-criticism to advance case formulation, prevention, and treatment in the field of eating disorders.

A call to action for more rigorous research on compassion-focused interventions for eating disorders: Commentary on Paranjothy and Wade (2024).

Paranjothy and Wade's (2024) meta-analysis identifying relations between self-criticism, self-compassion, and disordered eating prompted recommendations for augmenting existing front-line interventions with compassion-focused therapy (CFT) principles among self-critical individuals. While in theory this sounds promising, the reality is that the evidence supporting the use of CFT for eating disorders (EDs) is limited. I argue that before any clinical recommendations can made, more research is needed to better understand the utility of CFT, as well as what precise role self-criticism and self-compassion play in the context of intervention. In this commentary, I present three critical avenues for future research necessary to achieve this level of understanding. These include: (1) identifying moderators of response in clinical trials so that CFT can be safely delivered to those likely to benefit from this approach and avoided for those likely to experience harm; (2) establishing mediators of change so that we can understand whether CFT works through theory-specific or common mechanisms; and (3) testing the causal impact of intervention components so that knowledge on how to most effectively trigger the probable mediators of change can be gathered. This commentary will ideally spark further discussion, collaboration, and rigorous research dedicated to improving ED outcomes. PUBLIC SIGNIFICANCE: This commentary discusses the importance of further research dedicated towards enhancing understanding of the utility of compassion-focused interventions for eating disorders. It calls for more research on (1) testing moderators of response, (2) identifying mechanisms of change, and (3) establishing the most effective intervention components.

A case for integrating self-compassion interventions targeting shame and self-criticism into eating disorder treatment: Commentary on Paranjothy and Wade.

Paranjothy and Wade's (2024) meta-analysis revealed that disordered eating was robustly and consistently associated with greater self-criticism and lower self-compassion across samples. It is well known that even evidence-based treatments for eating disorders (EDs) do not produce long-lasting effects for many patients. Additionally, it is unclear whether existing "mainstream" evidence-based ED treatments effectively reduce shame and self-criticism and increase self-compassion, even when they intend to do so. In this commentary, we assert that Paranjothy and Wade's (2024) findings should inform the integration of self-compassion interventions within ED treatment. We argue that shame, a related but distinct construct, should be strongly considered as a primary intervention target in ED interventions that seek to reduce self-criticism and increase self-compassion. We hypothesize that directly addressing shame and bolstering self-compassion at the start of ED treatment may foster higher engagement and more durable effects. We introduce the potential for adjunctive self-compassion interventions to reduce shame and self-criticism, and enhance self-compassion, alongside or within existing ED treatments. Because self-criticism and shame are shared correlates of EDs and commonly co-occurring psychopathology, we contend with the possibility that self-compassion interventions may produce transdiagnostic effects. Shame, self-criticism, and self-compassion are important intervention targets to explore in future research.

A meta-analysis of disordered eating and its association with self-criticism and self-compassion.

OBJECTIVE: Future treatments for eating disorders (ED) need to be enhanced by targeting maintaining mechanisms. Literature suggests self-criticism and self-critical perfectionism act as key mechanisms exacerbating ED, and self-compassion protects against self-criticism. This meta-analysis examines associations between self-criticism and self-critical perfectionism on disordered eating (DE), and reviews how self-compassion and self-criticism relate to each other with respect to DE. METHOD: Searches across three databases yielded 135 studies across 42,952 participants. Heterogeneity, publication bias, and quality assessments were analyzed. Moderation analyses between self-criticism measures, self-compassion measures, between clinical and nonclinical samples, and between cross-sectional and experimental studies were also conducted. RESULTS: Random-effects models showed a medium positive link between self-criticism and DE (r = .37), and 10 subgroups pertaining to various measures of self-criticism utilized in literature showed small to large positive links with DE (r = .20-.52). Preliminary evidence also suggests negative relationships between self-compassion and DE (r = -.40 to -.43) and negative relationships between self-compassion and self-criticism (r = -.04 to -.88). DISCUSSION: Greater levels of self-criticism is linked with greater levels of DE and reduced levels of self-compassion, suggesting a need to tackle self-criticism and nurture self-compassion in standard treatments for ED. Understanding these interactions better in conjunction with dismantling intervention studies can help develop more effective and efficient interventions targeting self-criticism and self-compassion for people with DE. PUBLIC SIGNIFICANCE STATEMENT: Higher levels of self-criticism are linked with higher levels of DE and lower self-compassion. Self-compassion interventions could be more effective and efficient in reducing ED symptoms if self-criticism is tackled early in such treatments.

OBJETIVO: Los futuros tratamientos para los trastornos de la conducta alimentaria (TCA) deben ser mejorados mediante la focalización en los mecanismos de mantenimiento. La literatura sugiere que la autocrítica y el perfeccionismo autocrítico actúan como mecanismos clave que exacerban los TCA, y que la autocompasión protege contra la autocrítica. Este meta-análisis examina las asociaciones entre la autocrítica y el perfeccionismo autocrítico en la alimentación disfuncional (AD), y revisa cómo la autocompasión y la autocrítica se relacionan entre sí con respecto a la AD. MÉTODO: Las búsquedas en tres bases de datos arrojaron 135 estudios con 42,952 participantes. Se analizaron la heterogeneidad, el sesgo de publicación y las evaluaciones de calidad. También se llevaron a cabo análisis de moderación entre las medidas de autocrítica, las medidas de autocompasión, entre muestras clínicas y no clínicas, y entre estudios transversales y experimentales. RESULTADOS: Los modelos de efectos aleatorios mostraron una asociación positiva media entre la autocrítica y la AD (r = .37), y 10 subgrupos relacionados con diversas medidas de autocrítica utilizadas en la literatura mostraron asociaciones positivas pequeñas a grandes con la AD (r = .20-.52). Además, evidencia preliminar sugiere relaciones negativas entre la autocompasión y la AD (r = −0.40-−0.43) y relaciones negativas entre la autocompasión y la autocrítica (r = −.04-−.88). DISCUSIÓN: Los niveles mayores de autocrítica están relacionados con mayores niveles de AD y niveles reducidos de autocompasión, lo que sugiere la necesidad de abordar la autocrítica y fomentar la autocompasión en los tratamientos estándar para los TCA. Comprender mejor estas interacciones en conjunto con estudios de intervención puede ayudar a desarrollar intervenciones más efectivas y eficientes dirigidas a la autocrítica y la autocompasión para personas con AD.

Emotion coaching skills as an augmentation to family-based therapy for adolescents with anorexia nervosa: A pilot effectiveness study with families with high expressed emotion.

OBJECTIVE: To examine the feasibility and acceptability of augmenting family-based treatment (FBT) for adolescents with anorexia nervosa (AN) or atypical anorexia nervosa (AAN) with a parent emotion coaching intervention (EC) focused on reducing parent expressed emotion. METHOD: In this pilot effectiveness trial, families of adolescents with AN/AAN exhibiting high expressed emotion received standard FBT with either (1) EC group or (2) support group (an attention control condition focused on psychoeducation). RESULTS: Forty-one adolescents with AN or AAN were recruited (88% female, Mage = 14.9 ± 1.6 years, 95% White: Non-Hispanic, 1% White: Hispanic, 1% Bi-racial: Asian). Most study adolescents were diagnosed with AN (59%) while 41% were diagnosed with AAN. Participating parents were predominantly mothers (95%). Recruitment and retention rates were moderately high (76% and 71%, respectively). High acceptability and feasibility ratings were obtained from parents and interventionists with 100% reporting the EC intervention was "beneficial"-"very beneficial." The FBT + EC group demonstrated higher parental warmth scores at post-treatment compared to the control group (standardized effect size difference, d = 1.58), which was maintained at 3-month follow-up. Finally, at post-treatment, the FBT + EC group demonstrated higher rates of full remission from AN/AAN (40%) compared to FBT + support (27%), and were nine times more likely to be weight restored by 3-month follow-up. DISCUSSION: Augmenting FBT with emotion coaching for parents with high expressed emotion is acceptable, feasible, and demonstrates preliminary effectiveness. PUBLIC SIGNIFICANCE: Family based treatment for AN/AAN is the recommended treatment for youth but families with high criticism/low warmth are less likely to respond to this treatment. Adding a parent emotion coaching group (EC) where parents learn to talk to their adolescents about tough emotions is feasible and well-liked by families.

Differential correlates of criticism versus emotional overinvolvement towards patients with schizophrenia living in halfway houses or with their families.

PURPOSE: This study systematically searched for differential correlates of criticism vs. emotional overinvolvement (EOI) towards patients with schizophrenia in families and halfway houses, which have only incidentally been reported in previous research. Identified patterns were compared across settings. METHODS: We included 40 inpatients with schizophrenia living in halfway houses and 40 outpatients living with their families and recorded the expressed emotion (EE) of 22 psychiatric nurses or 56 parents, respectively, through Five Minutes Speech Samples. Each nurse rated 1-12 inpatients and each inpatient was rated by 2-5 nurses. Each outpatient was rated by one or both parents. As EE ratings had a multilevel structure, weighted Spearman correlations of criticism and EOI with various patient- and caregiver-related characteristics were calculated and compared with Meng's z-test. RESULTS: Criticism was weakly negatively correlated with EOI in nurses but negligibly in parents. Distinct patterns of significant differential correlates arose across settings. Outpatients' aggressive behavior and parents' related burden were mainly associated with higher criticism. Inpatients' symptoms (agitation/aggression, negative and other psychotic symptoms) and nurses' burnout (Depersonalization) were mainly associated with lower EOI. Inpatients' perceived criticism and outpatients' previous suicide attempts were equally associated with higher criticism and lower EOI (mirror correlations). Finally, various inpatient attributes (older age, chronicity, unemployment and smoking) triggered higher EOI only. Inpatients' age, psychopathology (esp. agitation/aggression and negative symptoms) and perceived criticism survived adjustment for multiple comparisons. CONCLUSION: Our findings suggest setting-specific pathogenetic pathways of criticism and EOI and might help customize psychoeducational interventions to staff and families.

Psychological Distress in Women with Fibromyalgia: The Roles of Body Appreciation, Self-Compassion, and Self-Criticism.

BACKGROUND: While past research detected a direct link between symptoms of fibromyalgia (FM) and psychological distress, body appreciation was suggested as a viable mediator of this link. The aim of the present study was to further develop an explanatory model for the effect of FM on women's psychological distress and identify possible protective and risk factors. Specifically, it was hypothesized that self-compassion would moderate the indirect effect of body appreciation and self-criticism on psychological distress in women with FM. METHOD: This study comprised a total of 293 women, aged 20-68 (M = 34.8, SD = 12.3), of whom 146 were women with FM and 147 were heathy controls. All the women completed questionnaires regarding demographic characteristics, depression (PHQ-9), anxiety (GAD-7), self-criticism (DEQ-SC), body appreciation (BAS2), and the self-compassion scale (SCS). RESULTS: A moderated serial mediation model demonstrated lower body appreciation in participants with FM compared to controls. These lower levels of body appreciation, together with lower levels of self-compassion, were associated with greater self-criticism and, consequently, higher levels of psychological distress. CONCLUSIONS: The results emphasize the role of self-compassion as a protective mechanism against psychological distress among women with FM. Future studies should further investigate the effect of self-compassion-focused interventions on patients with FM.

Social impediments to meat-eaters' adherence to critical calls for a meat-free diet: An experimental test of social norm and message source effects.

Reducing meat consumption is highly effective for reducing personal carbon emissions, yet most people in Western nations still eat meat. We build on recent research highlighting that group boundaries may impede dietary change by (a) promoting pro-meat norms and (b) prohibiting critical calls for a veg* diet (vegetarian and vegan, i.e., meat-free). Past research relied on self-reports and behavioural measures of engagement, leaving open whether these effects extend to food consumption settings and ad-hoc meal choice. We conducted two pre-registered experiments in which meat-eaters read critical calls to adopt a veg* diet, either by a vegan (outgroup) or a meat-eater (ingroup). In Experiment 2, participants moreover read an article either highlighting a veg* or a meat-eating norm. We then assessed actual (Experiment 1) or hypothetical (Experiment 2) meal choice as dependent variables. As predicted, intergroup criticism (i.e., voiced by veg*s) consistently led to message rejection in comparison to the same criticism voiced by meat eaters, but we did not observe effects on meal choice. Norms neither had a main nor interaction effect on self-reports and behaviour. We discuss potential intermediary processes between engagement with and adoption of a vegan diet and derive evidence-based recommendations for constructive communication across group boundaries.

Exploring the Relationship Between Instagram Use and Self-Criticism, Self-Compassion, and Body Dissatisfaction in the Spanish Population: Observational Study.

BACKGROUND: The widespread use of online social networks, particularly among the younger demographic, has catalyzed a growing interest in exploring their influence on users' psychological well-being. Instagram (Meta), a visually oriented platform, has garnered significant attention. Prior research has consistently indicated that Instagram usage correlates with heightened levels of perfectionism, body dissatisfaction, and diminished self-esteem. Perfectionism is closely linked to self-criticism, which entails an intense self-scrutiny and is often associated with various psychopathologies. Conversely, self-compassion has been linked to reduced levels of perfectionism and stress, while fostering greater positive affect and overall life satisfaction. OBJECTIVE: This study investigates the relationship between Instagram usage (time of use and content exposure) and users' levels of self-compassion, self-criticism, and body dissatisfaction. METHODS: This study comprised 1051 adult participants aged between 18 and 50 years, either native to Spain or residing in the country for at least a decade. Each participant completed a tailored questionnaire on Instagram usage, along with abbreviated versions of the Self-Compassion Scale, the Body Shape Questionnaire, and the Depressive Experiences Questionnaire, spanning from January 23 to February 25, 2022. RESULTS: A positive correlation was observed between daily Instagram usage and self-criticism scores. Participants of all age groups who spent over 3 hours per day on Instagram exhibited higher self-criticism scores than users who spent less than 1 hour or between 1 and 3 hours per day. Contrary to previous findings, no significant relationship was detected between Instagram usage time and levels of self-compassion or body dissatisfaction. Furthermore, content centered around physical appearance exhibited a positive correlation with self-criticism and body dissatisfaction scores. Among younger participants (aged 18-35 years), those who primarily viewed beauty or fashion content reported higher self-criticism scores than those consuming science-related content. However, this association was not significant for participants aged 35-50 years. Conversely, individuals who predominantly engaged with sports or fitness or family or friends content exhibited higher levels of body dissatisfaction than those focusing on science-related content. No significant associations were observed between self-compassion scores and daily Instagram usage or most-viewed content categories. CONCLUSIONS: The findings of this study underscore the considerable impact of Instagram usage on self-criticism and body dissatisfaction-2 variables known to influence users' psychological well-being and be associated with various symptoms and psychological disorders.

"I'm so dumb and worthless right now": factors associated with heightened momentary self-criticism in daily life.

Self-criticism is a trait associated with increased psychopathology, but self-criticism is also a personality state reflecting an action that people do in moments of time. In the current study, we explored factors associated with heightened self-criticism in daily life. Participants (N = 197) received five random prompts per day for one week on their mobile phones, where they reported their current affect (negative and positive affect), willpower self-efficacy, distress intolerance, degree of support and criticism from others, current context (location, activity, hunger, tiredness) and momentary self-criticism. We first demonstrated that self-criticism varies over time and across contexts, and is associated with heightened trait self-criticism. Then, using multilevel modelling, we explored the contextual factors associated with greater self-criticism. We found that self-criticism was higher when people were at home, and more tired. We also found higher self-criticism to be associated with greater negative and lower positive affect, greater distress intolerance, lower willpower and greater perceived criticism from others. In addition, self-criticism predicted subsequent distress intolerance, willpower and positive affect in lagged analyses. This study provides evidence that both environmental and psychological factors are associated with the dynamics of self-critical thoughts.

When nursing education becomes political: Norm-critical perspectives in a campus-based clinical learning environment.

Nursing education is in the process of incorporating critical thinking, social justice, and health inequality perspectives into educational structures, aspiring to help nursing students develop into professional nurses prepared to provide equal care. Norm criticism is a pedagogical philosophy that promotes social justice. This qualitative case study aimed to gain an understanding of and elaborate on an educational development initiative in which norm criticism was incorporated into the composition of a new campus-based clinical learning environment for nursing education. By analyzing documents and interviews with the help of reflexive thematic analysis three themes were generated: "Intention to educate beyond nursing education," "Educating in alliance with society," and "The educative ambiguity of the Clinical Learning Centre." The case study indicates that the incorporation of norm criticism into a campus-based clinical learning environment may encourage nursing students to evolve social skills for nursing practice that support health equality within healthcare. By collaborating with society, nursing education can considerably improve its educational frameworks in alignment with societal demands. However, the inclusion of norm criticism in a setting such as a campus-based clinical learning environment entails a clash with established institutionalized norms and being perceived as too proximate to politics.

Pandemic Forms.

Narrative structures, though invisible to the naked eye, guide our understanding of pandemics. Like curves and graphs, we can plot them, identify their patterns and organizing principles. These structures act upon our understanding of social and biological events just as much as the rhythms of viral replication and mutation. They order not only themselves but also social and health outcomes. This essay uses narrative precision to expand beyond Charles Rosenberg's influential dramaturgic model and develops new pandemic forms, scaled from the level of an individual line break to the multi-part series: Arc, a form of sequence. Cycle, a form of repetition. Sequel, a form of elongation. Caesura, a form of break. It investigates the potentialities and limitations of these forms, how they intersect, collide, and contradict, and how analysis of these interactions contributes to a deeper understanding of pandemics, their effects, and the diverse perspectives defining their structures. In doing so, it prototypes how literary methods offer conceptual frameworks for pandemic historiography and how a transdisciplinary, medical humanities analysis produces novel understandings at the intersection of health, culture, and society.

The Place of Religiosity and Spirituality in Frankl's Logotherapy: Distinguishing Salvific and Hygienic Objectives.

The relationship between psychology and religion has been widely debated in the field of psychology from its foundation as an empirical science to the present day. One author who was interested in the relationship between psychology and religion, the place of the latter in human nature, and its role in psychotherapy was the Viennese neurologist, psychiatrist, and philosopher Viktor Emil Frankl (1905-1997), the founder of logotherapy. This paper presents Frankl's main ideas about religion, the religious nature of the human being, and the relationship between religiosity, psychotherapy, and logotherapy, as well as a review of the main criticisms he has received in this regard. Frankl always defended the differences and limits between religion and psychotherapy, between the priestly cure of souls and the medical cure of souls, and between the salvific objective of religion and the hygienic objective of psychotherapy. In our opinion, critical authors have failed to appreciate Frankl's efforts to expose this distinction.

Pursuit-worthy research in health: Three examples and a suggestion.

This paper, in a nutshell, is a plea for community participation in research along with an adapted idea for how such participation should be shaped and understood. I will give varied examples of the ways in which scientists viewing a perceived problem solely from an external perspective has led to mistakes. If we do not properly take into account the knowledge and values of people with a condition, we are liable to pursue the wrong sorts of treatments. In particular, I provide examples of three ways (exemplified in the cases of "female hysteria", autism, and chronic fatigue syndrome) scientists are liable to pursue treatment of what they perceive to be at least partially mental illnesses that they/we shouldn't. I present the idea of deliberative research-the concept is based on that of deliberative democracy. The idea of deliberative democracy is that decisions should be made on the basis of reasons that would be acceptable to the target population. I similarly argue that research decisions should be made on the basis of reasons that would be acceptable to the target population, even if it requires other experts to determine how those reasons are best to be respected in the context of a particular project.

The eigen higher criticism and eigen Berk-Jones tests for multiple trait association studies based on GWAS summary statistics.

In this article, we propose the eigen higher criticism and the eigen Berk-Jones testing procedures to test the association between a single genetic variant and multiple correlated traits based on summary statistics from single-trait genome-wide association studies. Since the association pattern between each genetic variant and multiple traits varies across the whole genome, we further develop an omnibus (OMNI) test using the aggregated Cauchy association test to achieve more robust performance. The p values of our proposed tests can be computed analytically, thus, our methods are appealing in large-scale multiple phenotype association studies. Through extensive simulation studies, we found that all of our proposed tests can maintain the correct type I error rates and our proposed tests have greater power in certain settings. In addition, the OMNI test can always provide robust power performance across a wide range of scenarios. We apply the proposed tests to the Global Lipids Genetics Consortium summary statistics data set and identify additional genetic variants that were missed by the original single-trait analyses. We also develop an R package EBMMT publicly available at https://github.com/Vivian-Liu-Wei64/EBMMT.

Functional connectivity of cognition-related brain networks in adults with fetal alcohol syndrome.

BACKGROUND: Fetal alcohol syndrome (FAS) can result in cognitive dysfunction. Cognitive functions affected are subserved by few functional brain networks. Functional connectivity (FC) in these networks can be assessed with resting-state functional MRI (rs-fMRI). Alterations of FC have been reported in children and adolescents prenatally exposed to alcohol. Previous reports varied substantially regarding the exact nature of findings. The purpose of this study was to assess FC of cognition-related networks in young adults with FAS. METHODS: Cross-sectional rs-fMRI study in participants with FAS (n = 39, age: 20.9 ± 3.4 years) and healthy participants without prenatal alcohol exposure (n = 44, age: 22.2 ± 3.4 years). FC was calculated as correlation between cortical regions in ten cognition-related sub-networks. Subsequent modelling of overall FC was based on linear models comparing FC between FAS and controls. Results were subjected to a hierarchical statistical testing approach, first determining whether there is any alteration of FC in FAS in the full cognitive connectome, subsequently resolving these findings to the level of either FC within each network or between networks based on the Higher Criticism (HC) approach for detecting rare and weak effects in high-dimensional data. Finally, group differences in single connections were assessed using conventional multiple-comparison correction. In an additional exploratory analysis, dynamic FC states were assessed. RESULTS: Comparing FAS participants with controls, we observed altered FC of cognition-related brain regions globally, within 7 out of 10 networks, and between networks employing the HC statistic. This was most obvious in attention-related network components. Findings also spanned across subcomponents of the fronto-parietal control and default mode networks. None of the single FC alterations within these networks yielded statistical significance in the conventional high-resolution analysis. The exploratory time-resolved FC analysis did not show significant group differences of dynamic FC states. CONCLUSIONS: FC in cognition-related networks was altered in adults with FAS. Effects were widely distributed across networks, potentially reflecting the diversity of cognitive deficits in FAS. However, no altered single connections could be determined in the most detailed analysis level. Findings were pronounced in networks in line with attentional deficits previously reported.

Expressed emotion and treatment outcome in higher levels of care for eating disorders.

OBJECTIVE: Expressed emotion (EE) among caregivers toward the affected offspring is a negative prognostic indicator for adolescent patients with eating disorders (EDs) in outpatient treatment. Less research has examined its impact on adolescents in higher levels of care (HLOC). The current study examined differences in caregiver EE according to the subtype of anorexia nervosa (AN) (restricting [AN-R] versus binge/purge [AN-BP]), and level of care (LOC). We also examined the main effects of baseline caregiver EE (emotional overinvolvement [EOI] or criticism), AN subtype, and their interaction on eating pathology and depression at discharge. METHOD: Adolescent patients (N = 203) receiving treatment at HLOCs completed measures of ED pathology (Eating Disorder Examination-Questionnaire) and depression (Patient Health Questionnaire-9) at baseline and discharge, and one caregiver of each patient completed a measure of EE (Family Questionnaire) at baseline. RESULTS: No differences in caregiver EE were found between patients with AN-R versus AN-BP, or relative to LOC. Caregiver EE did not predict outcome for ED symptoms or depression at discharge. DISCUSSION: The impact of high caregiver EE may be less substantial at HLOCs than outpatient care given that caregivers are less involved in treatment at HLOCs. Future research is needed to determine if high caregiver EOI leads to poor treatment outcome for adolescents as it does for adults, or whether it is an appropriate expression of care for patients who are ill enough to require HLOC treatment. PUBLIC SIGNIFICANCE STATEMENT: High caregiver EE was not found to predict treatment outcome for adolescents with eating disorders in higher levels of care (HLOCs), possibly due to the limited involvement of caregivers in HLOCs. However, patients step down to outpatient treatment, where high caregiver EE can have a significant negative impact on outcome. HLOCs should incorporate efforts to reduce high caregiver EE in anticipation of step-down to outpatient treatment.