Background There is a lack of research examining whether childhood abuse affects the quality of life (QoL) of individuals living with bipolar disorder and its improvement over the course of treatment.Methods Data from the Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder were used to explore the associations between childhood abuse and multiple domains of QoL among 476 outpatients with bipolar disorder. Rates of change in QoL throughout treatment were explored with a series of Generalised Estimation Equations for repeated measures.Results At baseline, childhood abuse was related to poorer QoL in the domains of subjective feelings of wellbeing, social relationships and general activities-but not in physical health or leisure activities. Throughout treatment, participants with a history of childhood abuse reported significantly worse QoL in the same domains, than participants with no history of childhood abuse. Interestingly, exploratory analyses showed that participants with a history of childhood abuse and a current diagnosis of post-traumatic stress disorder (PTSD) had significantly worse QoL in all domains, than participants with no history of childhood abuse or diagnosis of PTSD. There were no significant differences between groups in change in QoL in any of the domains.Conclusion This study comprehensively investigated the relationships between a history of childhood abuse and QoL among people with bipolar disorder who were receiving pharmacotherapy. Although the present findings need to be replicated, they suggest significant impairment in several domains of QoL associated with childhood abuse, which has service and treatment implications for trauma-informed care.Trial Registration ClinicalTrials.gov identifier: NCT01331304

Bipolar disorder is associated with increased mortality from cardiovascular disease, incidence of Metabolic Syndrome (MetS), and obesity. Adverse childhood experiences (ACEs) may contribute to this increased incidence, but findings have been mixed. We aimed to determine associations between ACEs and cardiometabolic risk markers in people with bipolar disorder, and how they change during pharmacological treatment. Data was analysed from 482 participants with bipolar disorder treated for 24 weeks with lithium or quetiapine, comparing those with and without ACEs across cardiometabolic markers. At baseline, those with ACEs had higher body mass indexes but were similar on all other cardiometabolic measures. During the 24-week treatment period, those with ACEs improved slightly more on continuous metabolic syndrome score (cMetS; p = .004), waist circumference, (p = .041) high density lipoproteins (HDL) cholesterol, (p = .028) and diastolic blood pressure (p = .042) than those without ACEs. Sensitivity analysis exploring the role of ACE type revealed that change in HDL was most strongly associated with sexual abuse; higher diastolic blood pressure with emotional abuse; and increased waist circumference with emotional and physical abuse, and higher cMetS with all three ACE types. There were almost no baseline differences in cardiometabolic markers between the ACE and no ACE groups. Those with ACEs seemingly benefitted more from psychiatric treatment regarding their cardiovascular health compared to the no ACE group. Future research should explore links between ACEs and cardiovascular health in those with bipolar disorder, including benefits of psychiatric treatment, the role of specific ACE types, and longer-term outcomes.

Background Avoidant/restrictive food intake disorder (ARFID) leads to faltering growth and psychosocial impairment. Three phenotypes can co-occur: fear of aversive consequences of eating (ARFID-fear phenotype), sensory sensitivity, and lack of interest in eating/food. We hypothesized that youth with ARFID, especially ARFID-fear phenotype, would show hyperactivation of fear-related regions in response to ARFID-specific fear images, compared to healthy controls (HC), and activation of these regions would positively correlate with ARFID fear severity.Methods Youth (N=103: 76 ARFID, including 20 ARFID-fear phenotype; 27 HC) underwent functional MRI scanning while viewing ARFID-specific fear (e.g. vomiting, choking) versus neutral images. We compared blood-oxygen-level-dependent (BOLD) response in fear-related region of interests (ROI; e.g. amygdala, hippocampus, insula) between ARFID and ARFID-fear phenotype versus HC. We evaluated the association between brain response and ARFID fear severity in ARFID-fear phenotype.Results Across individuals, there was a robust bilateral amygdala response to ARFID-specific fear versus neutral images. Compared to HC, ARFID-fear phenotype showed a greater insula response to ARFID-specific fear versus neutral images (p=0.049). There were no other group differences and no significant relationships between BOLD response and ARFID fear severity in ARFID-fear phenotype.Conclusions ARFID-specific fear images elicit amygdala responses across individuals, with greater activation in the insula only in ARFID-fear phenotype versus HC. These findings validate the ARFID-specific fear paradigm and highlight the intriguing possibility that, in the ARFID-fear phenotype, universally feared experiences such as choking and vomiting serve as the unconditioned stimulus in developing ARFID and may partially be mediated by the insular cortex.

Disclosure: M. Wronski: None. A. Shreekumar: None. M. Bredella: None. L. Kerem: None. T. Deckersbach: None. K. Holman: None. S.E. Smith: None. E. Asanza: None. F. Plessow: Dr. Plessow is an inventor on US provisional patent application no. 63/467,980 (Oxytocin-based therapeutics to improve cognitive control in individuals with attention deficit hyperactivity disorder). L.M. Holsen: None. E.A. Lawson: Dr. Lawson receives grant support and research study drug from Tonix Pharmaceuticals and receives royalties from UpToDate, Dr. Lawson and/or immediate family member holds stock in Thermo Fisher Scientific, Zoetis, Danaher Corporation, Intuitive Surgical, Merck and West Pharmaceutical Services, Dr. Lawson is an inventor on US provisional patent application no. 63/467,980 (Oxytocin-based therapeutics to improve cognitive control in individuals with attention deficit hyperactivity disorder. Objective: Oxytocin (OXT), a hypothalamic hormone secreted into brain regions regulating eating behavior and metabolism, is under investigation as an anti-obesity therapeutic. In animals and humans, OXT administration reduces caloric intake, and a pilot functional MRI (fMRI) study in 10 men with overweight/obesity showed that single-dose intranasal (IN) OXT reduced food-related activation in reward (ventral tegmental area, VTA; orbitofrontal cortex, OFC; anterior insula, aINS) and homeostatic (hypothalamus) brain regions, while increasing activation in a cognitive control area (dorsal anterior cingulate cortex, dACC). There are no data regarding the mechanisms underlying the anorexigenic effects of chronic OXT administration in humans. In a trial of IN OXT in adults with obesity (NCT03043053), we hypothesized that 4-week IN OXT would similarly reduce brain activation in food reward and homeostatic regions while increasing activation in cognitive control regions. Methods: Sixty-one non-diabetic adults with obesity were randomized 1:1 to 24 IU IN OXT 4x/day or placebo; of these, 58 had usable MRI data. OXT was held on the morning of visits. In a 3T Skyra scanner, participants completed a visual food cue paradigm and a stop signal task (SST), assessing neural response to food stimuli and inhibitory control, respectively, at baseline and week 4 visits. We used Statistical Parametric Mapping for quality control and first-level modeling of fMRI data, MarsBaR for β extraction, and R for second-level models. Linear mixed-effects models, incorporating a treatment-by-visit interaction term, were applied to examine OXT vs placebo effects on fMRI activation for predefined contrasts and regions of interest (food cue: VTA, OFC, aINS, hypothalamus; SST: dorsolateral prefrontal cortex [dlPFC], dACC, anterior supplementary motor cortex [preSMA]). Results: Treatment groups (OXT n=30, placebo 28) did not differ in sex (OXT 17 [56.7%], placebo 15 [53.6%] female), age (OXT mean±se=33.7±1.1, placebo 32.8±1.2 years), and BMI (OXT 36.6±0.7, placebo 36.2±0.8 kg/m2). Four-week IN OXT vs placebo reduced fMRI activation in aINS (F=3.69, p=0.028, d=0.28) in response to high-calorie food cues vs objects; and in OFC (F=4.71, p=0.016, d=0.36), aINS (F=3.07, p=0.041, d=0.26), and hypothalamus (F=9.85, p=0.001, d=0.51) in response to low-calorie foods vs objects. Four-week IN OXT vs placebo increased activation in dACC (F=3.16, p=0.040, d=0.37) and preSMA (F=2.81, p=0.049, d=0.35) during successful vs failed SST response inhibition. Conclusion: We found that prolonged IN OXT administration (in the absence of acute OXT effects as drug was not given on morning of visits) attenuated fMRI activation of reward and homeostatic brain areas while enhancing activation of cognitive control-related regions, providing potential neural mechanisms for anorexigenic effects of exogenous OXT in obesity. Presentation: Monday, July 14, 2025

Importance The neurobiology of avoidant/restrictive food intake disorder (ARFID) is poorly understood. Objective To evaluate whether individuals with ARFID exhibit disruptions in fear, appetite, and disgust brain regions compared with healthy control (HC) participants when shown images of food and objects. Design, Setting, and Participants In this case-control study conducted from July 2016 to January 2021, children, adolescents, and young adults completed structured interviews and a validated functional magnetic resonance imaging (fMRI) food cue paradigm. The study was conducted at a single academic medical center. Data analysis was conducted from April 2023 to August 2024. Exposures Presence vs absence of ARFID and its phenotypes (ARFID-fear, ARFID–lack of interest in eating, ARFID–sensory sensitivity); pictures of food vs objects during fMRI food cue paradigm. Main Outcomes and Measures Blood oxygenation level–dependent activation in regions of interest (ROIs; amygdala, hypothalamus, insula, anterior cingulate cortex [ACC]) and the whole brain. Results Participants were 110 children, adolescents, and young adults with full or subthreshold ARFID (75 participants; mean [SD] age, 16.2 [3.8] years; 41 [55%] female) and age-matched HC participants (35 participants; mean [SD] age, 17.3 [4.0] years; 27 [69%] female) recruited for studies of the neurobiology of ARFID and restrictive eating disorders. Participants with ARFID demonstrated greater activation than HC participants of the ACC (mean difference, 0.48 [95% CI, 0.19 to 0.77]; P = .009), sensory association cortex (mean difference on left side, 0.54 [95% CI, 0.29 to 0.79]; P = .005; right side, 0.52 [95% CI, 0.28 to 0.76]; P = .02), and supplementary motor cortex (mean difference, 0.81 [95% CI, 0.47 to 1.15]; P = .04). The ARFID-fear group showed greater amygdala activation vs HC (mean difference, 0.49 [95% CI, 0.16 to 0.82]; P = .04), and greater lack of interest was associated with lower hypothalamus activation in the ARFID–lack of interest group ( r = −0.38 [95% CI, −0.69 to −0.11]; P = .03). The ARFID–sensory sensitivity group did not show greater insula activation vs HC but showed greater activation of the ACC (mean difference, 0.48 [95% CI, 0.22 to 0.74]; P = .005) and somatosensory cortex (mean difference on left side, 0.60 [95% CI, 0.33-0.87]; P = .001; right side, 0.54 [95% CI, 0.29 to 0.80]; P = .03). Conclusions and Relevance Results indicate generalized hyperactivation of ACC, sensory association cortex, and supplementary motor cortex in response to visual food stimuli in children, adolescents, and young adults with ARFID, suggesting a novel neurobiological circuit associated with this disorder. Activation appears consistent with ARFID phenotypic rationales for food avoidance, with hyperactivation of fear regions in ARFID-fear and hypoactivation of appetite regions with increasing ARFID–lack of interest severity.

Trichotillomania (TTM) is associated with impairments in response inhibition and cognitive flexibility, but it is unclear how such impairments relate to treatment outcome. The present study examined pre-treatment response inhibition and cognitive flexibility as predictors of treatment outcome, change in these domains from pre- to post-treatment, and associations with TTM severity. Participants were drawn from a randomized controlled trial comparing acceptance-enhanced behavior therapy (AEBT) to psychoeducation and supportive therapy (PST) for TTM. Adults completed assessments at pre-treatment (n=88) and following 12 weeks of treatment (n=68). Response inhibition and cognitive flexibility were assessed using the Stop Signal Task and Object Alternation Task, respectively. Participants completed the MGH-Hairpulling Scale. Independent evaluators administered the NIMH-Trichotillomania Severity Scale and Clinical Global Impressions-Improvement Scale. Higher pre-treatment TTM severity was associated with poorer pre-treatment cognitive flexibility, but not response inhibition. Better pre-treatment response inhibition performance predicted positive treatment response and lower post-treatment TTM symptom severity, irrespective of treatment assignment. Cognitive flexibility did not predict treatment response. After controlling for age, neither neurocognitive variable changed during treatment. Response inhibition and cognitive flexibility appear uniquely related to hair pulling severity and treatment response in adults with TTM. Implications for treatment delivery and development are discussed.

The impact of childhood abuse on the presentation of bipolar disorder could be further elucidated by comparing the networks of affective symptoms among individuals with and with no history of childhood abuse. Data from 476 participants in the Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study were used to fit several regularised Gaussian Graphical Models. Differences in the presentation of depressive and manic symptoms were uncovered: only among participants with a history of childhood abuse, inadequacy and pessimism were central symptoms in the network of depressive symptoms, while racing thoughts was an important symptom in the network of manic symptoms. Following network theory, focusing treatments at the symptom-level and on central symptoms - like inadequacy, pessimism, , and racing thoughts - could be an effective approach for managing affective symptoms among the sizeable proportion of people with bipolar disorder who have experienced childhood abuse. This study contributes a thorough investigation of the networks of affective symptoms among participants with and with no history of childhood abuse, albeit limited by the use of a binary, self-report measure of childhood abuse, thereby emphasising the importance of assessing for childhood abuse and taking needed steps towards identifying novel targets for treating bipolar disorder.

Background: Current noninvasive brain stimulation methods are incapable of directly modulating subcortical brain regions critically involved in psychiatric disorders. Transcranial Focused Ultrasound (tFUS) is a newer form of noninvasive stimulation that could modulate the amygdala, a subcortical region implicated in fear. Objective: We investigated the effects of active and sham tFUS of the amygdala on fear circuit activation, skin conductance responses (SCR), and self-reported anxiety during a fear-inducing task. We also investigated amygdala tFUS’ effects on amygdala-fear circuit resting-state functional connectivity. Methods: Thirty healthy individuals were randomized in this double-blinded study to active or sham tFUS of the left amygdala. We collected fMRI scans, SCR, and self-reported anxiety during a fear-inducing task (participants viewed red or green circles which indicated the risk of receiving an aversive stimulus), as well as resting-state scans, before and after tFUS. Results: Compared to sham tFUS, active tFUS was associated with decreased (pre to post tFUS) blood-oxygen-level-dependent fMRI activation in the amygdala (F(1,25) = 4.86, p = 0.04, η2 = 0.16) during the fear task, and lower hippocampal (F(1,27) = 4.41, p = 0.05, η2 = 0.14), and dorsal anterior cingulate cortex (F(1,27) = 6.26, p = 0.02; η2 = 0.19) activation during the post tFUS fear task. The decrease in amygdala activation was correlated with decreased subjective anxiety (r = 0.62, p = 0.03). There was no group effect in SCR changes from pre to post tFUS (F(1,23) = 0.85, p = 0.37). The active tFUS group also showed decreased amygdala-insula (F(1,28) = 4.98, p = 0.03) and amygdala-hippocampal (F(1,28) = 7.14, p = 0.01) rsFC, and increased amygdala-ventromedial prefrontal cortex (F(1,28) = 3.52, p = 0.05) resting-state functional connectivity. Conclusions: tFUS can change functional connectivity and brain region activation associated with decreased anxiety. Future studies should investigate tFUS’ therapeutic potential for individuals with clinical levels of anxiety.

Introduction: Depressed individuals are more likely to die from cardiovascular disease (CVD) than those without depression. People with CVD have higher rates of depression than those without and have higher mortality rates if they have comorbid depression. While physical activity (PA) improves both, few people engage in enough. We compared self-guided internet-based cognitive behavior therapy (CBT) + Fitbit or mindfulness-based cognitive therapy (MBCT) + Fitbit, with Fitbit only to increase daily steps for participants with depression who have low PA.Methods: Adult participants (N = 340) were recruited from two online patient-powered research networks and randomized to one of three study interventions for 8 weeks with an additional 8 weeks of follow-up. Using linear mixed effects models, we evaluated the effect of the intervention on average daily steps (NCT03373110).Results: Average daily steps increased 2.8 steps per day in MBCT+Fitbit, 2.9 steps/day in CBT + Fitbit, but decreased 8.2 steps/day in Fitbit Only. These changes were not statistically different between the MBCT+Fitbit and CBT + Fitbit groups, but were different from Fitbit Only across the initial 8-week period. Group differences were not maintained across follow-up. Exploratory analyses identified comorbid anxiety disorders, self-reported PA, and employment status as moderators.Discussion: Changes in daily steps over both 8-and 16-week periods-regardless of intervention group-were minimal. The results emphasize the limits of using self-guided web-based psychotherapy with an activity tracker to increase PA in participants with a history of depression and low PA.

Objective.Anxiety can interfere with attention and working memory, which are components that affect learning. Statistical models have been designed to study learning, such as the Bayesian Learning Model, which takes into account prior possibilities and behaviours to determine how much of a new behaviour is determined by learning instead of chance. However, the neurobiological basis underlying how anxiety interferes with learning is not yet known. Accordingly, we aimed to use neuroimaging techniques and apply a Bayesian Learning Model to study learning in individuals with generalised anxiety disorder (GAD). Methods.Participants were 25 controls and 14 individuals with GAD and comorbid disorders. During fMRI, participants completed a shape-button association learning and reversal task. Using a flexible factorial analysis in SPM, activation in the dorsolateral prefrontal cortex, basal ganglia, and hippocampus was compared between groups during first reversal. Beta values from the peak of these regions were extracted for all learning conditions and submitted to repeated measures analyses in SPSS. Results.Individuals with GAD showed less activation in the basal ganglia and the hippocampus only in the first reversal compared with controls. This difference was not present in the initial learning and second reversal. Conclusion.Given that the basal ganglia is associated with initial learning, and the hippocampus with transfer of knowledge from short- to long-term memory, our results suggest that GAD may engage these regions to a lesser extent during early accommodation or consolidation of learning, but have no longer term effects in brain activation patterns during subsequent learning.

Bipolar disorder is a mood disorder characterized by recurrent hypomanic/manic and/or depressive mood episodes. Although mood-stabilizing medication is the first line of treatment for bipolar disorder, the beneficial effects of empirically supported, cognitive behavioral-based psychosocial treatments have been recognized. In this chapter, we review the clinical presentation and diagnosis of bipolar disorder, as well as its assessment and treatment. We describe cognitive behavioral strategies that can be used independently or in tandem with medications to treat the different phases of the illness and review the empirical support for cognitive behavioral treatments for bipolar disorder. We conclude with a case vignette to illustrate how cognitive behavioral-based psychosocial treatments can be used in the treatment of bipolar disorder.

Anorexia nervosa (AN) and atypical AN (AtypAN) are complex neurobiological illnesses that typically onset in adolescence with an often treatment-refractory and chronic illness trajectory. Aberrant eating behaviors in this population have been linked to abnormalities in food reward and cognitive control, but prior studies have not examined respective contributions of clinical characteristics and metabolic state. Research is needed to identify specific disruptions and inform novel intervention targets to improve outcomes. Fifty-nine females with AN ( n = 34) or AtypAN ( n = 25), ages 10–22 years, all ≤90% expected body weight, and 34 age-matched healthy controls (HC) completed a well-established neuroimaging food cue paradigm fasting and after a standardized meal, and we used ANCOVA models to investigate main and interaction effects of Group and Appetitive State on blood oxygenation level-dependent (BOLD) activation for the contrast of exposure to high-calorie food images minus objects. We found main effects of Group with greater BOLD activation in the dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex (DLPFC), hippocampus, caudate, and putamen for AN/AtypAN versus HC groups, and in the three-group model including AN, AtypAN, and HC (sub-)groups, where differences were primarily driven by greater activation in the AtypAN subgroup versus HC group. We found a main effect of Appetitive State with increased premeal BOLD activation in the hypothalamus, amygdala, nucleus accumbens, and caudate for models that included AN/AtypAN and HC groups, and in BOLD activation in the nucleus accumbens for the model that included AN, AtypAN, and HC (sub-)groups. There were no interaction effects of Group with Appetitive State for any of the models. Our findings demonstrate robust feeding-state independent group effects reflecting greater neural activation of specific regions typically associated with reward and cognitive control processing across AN and AtypAN relative to healthy individuals in this food cue paradigm. Differential activation of specific brain regions in response to the passive viewing of high-calorie food images may underlie restrictive eating behavior in this clinical population.

Background Diseases that affect fewer than 2000 people in the general population are defined as rare diseases [1]. The rarity and the associated limited experience with these diseases, but also the large number of about 8000 rare diseases [2], pose a major diagnostic challenge for physicians.On average, affected patients need 5.6 to 7.6 years until they receive a diagnosis and thus the correct therapy [3].These diagnostic odysseys place a heavy financial, health, and psychological burden both on patients and their families.Diagnostic decision support systems (DDSS) have great potential to assist physicians in diagnostic decision-making and can indicate the presence of a rare disease much earlier. An exploratory study conducted at the Outpatient Clinic for Rare Inflammatory Systemic Diseases with Renal Involvement at Hannover Medical School showed that the diagnostic process can be shortened by a DDSS. The median lead between diagnosis and the hypothetical time of diagnosis by a DDSS was three months [4]. A follow-up study showed that health economic savings were also possible by making the diagnosis so early [5]. Objectives Measured against the hypothetical diagnosis time points determined in the previous study [4], this study aimed to investigate, in the same patient population, the extent to which earlier diagnosis using a DDSS would have influenced patients' quality of life (QOL). Methods To determine the potential for improving QOL through artificial intelligence (AI), 71 patients from the patient cohort of the previous studies were surveyed [4][5].The questionnaire was composed of established questionnaires such as the WHO HPQ and the SF-36.In five interview sessions from the onset of the disease, the time of professional diagnosis, to the current time, the development of QOL was retrospectively recorded. To analyze the development of QOL during the disease, but also to show the influence of the DDSS on QOL, data were also collected for the time points at which the DDSS would have indicated the correct diagnosis as the first suggestion or among the first five suggestions.Statistical analysis, graphical presentation and interpretation of the questionnaires were performed using statistical software. Results The study showed that the QOL of most patients improved with a correct diagnosis. The graphically depicted progression of the patients' health perception are shown in Figure 1: with the onset of the first symptoms, 65% of the patients found their state of health to be less good or bad, in course of disease, this number increased to 70%. At the current time, the time of the interviews, the number declined to 28%. Originally, no patient was in excellent health, but at the current condition after the diagnostic odyssey, 10% were able to describe their state of health as excellent. The interviews show an overall decline in well-being during the diagnostic odyssey, which slowly increases with the correct diagnosis. Conclusion The study showed how much a correct diagnosis affects the patients' QOL. The use of a DDSS would have significantly shortened the diagnostic odysseys and thus improved patients' QOL at an earlier stage. References [1]Blöß S, et al (2017) Diagnostic needs for rare diseases and shared prediagnostic phenomena: Results of a German-wide expert Delphi survey. PLoS One 12:e0172532[2]https://www.bundesgesundheitsministerium.de/fileadmin/Dateien/3_Downloads/N/NAMSE/National_Plan_of_Action.pdf. Accessed 15 Jan 2023[3]https://globalgenes.org/wp-content/uploads/2013/04/ShireReport-1.pdf. Accessed 15 Jan 2023[4]Ronicke S, et al (2019) Can a decision support system accelerate rare disease diagnosis? Evaluating the potential impact of Ada DX in a retrospective study. Orphanet J Rare Dis 14:69[5]Willmen T, et al (2021) Health economic benefits through the use of diagnostic support systems and expert knowledge. BMC Health Serv Res 21:947 Acknowledgements: NIL. Disclosure of Interests None Declared.Figure 1Retrospective development of health perception over the course of the disease among the study participants (n=71). Displayed are the results as an extract of the SF-36.

The default mode network (DMN) is a network of brain regions active during rest and self-referential thinking. Individuals with major depressive disorder (MDD) show increased or decreased DMN activity relative to controls. DMN activity has been linked to a tendency to ruminate in MDD. It is unclear if individuals who are at risk for, but who have no current or past history of depression, also show differential DMN activity associated with rumination. We investigated whether females with high levels of neuroticism with no current or lifetime mood or anxiety disorders (n = 25) show increased DMN activation, specifically when processing negative self-referential information, compared with females with average levels of neuroticism (n = 28). Participants heard criticism and praise during functional magnetic resonance imaging (MRI) scans in a 3T Siemens Prisma scanner. The at-risk group showed greater activation in two DMN regions, the medial prefrontal cortex and the inferior parietal lobule (IPL), after hearing criticism, but not praise (relative to females with average levels of neuroticism). Criticism-specific activation in the IPL was significantly correlated with rumination. Individuals at risk for depression may, therefore, have an underlying neurocognitive vulnerability to use a brain network typically involved in thinking about oneself to preferentially ruminate about negative, rather than positive, information.

Transcranial focused ultrasound (tFUS) is a novel noninvasive brain stimulation method that can target brain tissue millimeters in the diameter anywhere in the brain. This superior spatial and depth specificity enables the neuromodulation of deeper subcortical brain regions previously inaccessible by other noninvasive methods. The amygdala is a deeper brain region that plays a central role in fear processing. We investigated whether tFUS of the amygdala could change neural and subjective measures of fear.

Background Mindfulness can improve overall well-being by training individuals to focus on the present moment without judging their thoughts. However, it is unknown how much mindfulness practice and training are necessary to improve well-being. Objective The primary aim of this study was to determine whether a standard 8-session web-based mindfulness-based cognitive therapy (MBCT) program, compared with a brief 3-session mindfulness intervention, improved overall participant well-being. In addition, we sought to explore whether the treatment effects differed based on the baseline characteristics of the participants (ie, moderators). Methods Participants were recruited from 17 patient-powered research networks, web-based communities of stakeholders interested in a common research area. Participants were randomized to either a standard 8-session MBCT or a brief 3-session mindfulness training intervention accessed on the web. The participants were followed for 12 weeks. The primary outcome of the study was well-being, as measured by the World Health Organization—Five Well-Being Index. We hypothesized that MBCT would be superior to a brief mindfulness training. Results We randomized 4411 participants, 3873 (87.80%) of whom were White and 3547 (80.41%) of female sex assigned at birth. The mean baseline World Health Organization—Five Well-Being Index score was 50.3 (SD 20.7). The average self-reported well-being in each group increased over the intervention period (baseline to 8 weeks; model-based slope for the MBCT group: 0.78, 95% CI 0.63-0.93, and brief mindfulness group: 0.76, 95% CI 0.60-0.91) as well as the full study period (ie, intervention plus follow-up; baseline to 20 weeks; model-based slope for MBCT group: 0.41, 95% CI 0.34-0.48; and brief mindfulness group: 0.33, 95% CI 0.26-0.40). Changes in self-reported well-being were not significantly different between MBCT and brief mindfulness during the intervention period (model-based difference in slopes: −0.02, 95% CI −0.24 to 0.19; P=.80) or during the intervention period plus 12-week follow-up (−0.08, 95% CI −0.18 to 0.02; P=.10). During the intervention period, younger participants (P=.05) and participants who completed a higher percentage of intervention sessions (P=.005) experienced greater improvements in well-being across both interventions, with effects that were stronger for participants in the MBCT condition. Attrition was high (ie, 2142/4411, 48.56%), which is an important limitation of this study. Conclusions Standard MBCT improved well-being but was not superior to a brief mindfulness intervention. This finding suggests that shorter mindfulness programs could yield important benefits across the general population of individuals with various medical conditions. Younger people and participants who completed more intervention sessions reported greater improvements in well-being, an effect that was more pronounced for participants in the MBCT condition. This finding suggests that standard MBCT may be a better choice for younger people as well as treatment-adherent individuals. Trial Registration ClinicalTrials.gov NCT03844321; https://clinicaltrials.gov/ct2/show/NCT03844321

Given the limited treatment options for trichotillomania (TTM), or Hair Pulling Disorder, this large randomized clinical trial evaluated the efficacy of acceptance-enhanced behavior therapy for TTM (AEBT-TTM) in reducing TTM severity relative to psychoeducation and supportive therapy (PST). Eighty-five adults (78 women) with TTM received 10 sessions (over 12 weeks) of either AEBT-TTM or PST. Independent evaluators masked to treatment assignment assessed participants at baseline (week 0), midpoint (week 6), and endpoint (week 12). Consistent with a priori hypotheses, 64% of the adults treated with AEBT-TTM were classified as clinical responders at post-treatment relative to 38% treated with PST. Clinical responders were identified by a score of 1 or 2 on the Clinical Global Impressions-Improvement (CGI-I) scale. Relative to the PST group, the AEBT-TTM group demonstrated significantly greater pre-to post-treatment reductions on the self-report Massachusetts General Hospital-Hairpulling Scale (MGH-HS) and the evaluator-rated National Institute of Mental Health Trichotillomania Severity Scale (NIMH-TSS). There were no significant post-treatment group differences on the Clinical Global Impressions-Severity (CGI-S) scale, or rate of TTM diagnoses. Results suggest AEBT-TTM provides greater treatment benefit than PST. Future research should continue to investigate AEBT-TTM along with mediators and moderators of its efficacy.