TGF-ß-mediated silencing of genomic organizer SATB1 promotes Tfh cell differentiation and formation of intra-tumoral tertiary lymphoid structures.

The immune checkpoint receptor PD-1 on T follicular helper (Tfh) cells promotes Tfh:B cell interactions and appropriate positioning within tissues. Here, we examined the impact of regulation of PD-1 expression by the genomic organizer SATB1 on Tfh cell differentiation. Vaccination of CD4CreSatb1f/f mice enriched for antigen-specific Tfh cells, and TGF-ß-mediated repression of SATB1 enhanced Tfh differentiation of human T cells. Mechanistically, high Icos expression in Satb1-/- CD4+ T cells promoted Tfh cell differentiation by preventing T follicular regulatory cell skewing and resulted in increased isotype-switched B cell responses in vivo. Ovarian tumors in CD4CreSatb1f/f mice accumulated tumor antigen-specific, LIGHT+CXCL13+IL-21+ Tfh cells and tertiary lymphoid structures (TLS). TLS formation decreased tumor growth in a CD4+ T cell and CXCL13-dependent manner. The transfer of Tfh cells, but not naive CD4+ T cells, induced TLS at tumor beds and decreased tumor growth. Thus, TGF-ß-mediated silencing of Satb1 licenses Tfh cell differentiation, providing insight into the genesis of TLS within tumors.

Ago2-Dependent Processing Allows miR-451 to Evade the Global MicroRNA Turnover Elicited during Erythropoiesis.

MicroRNAs (miRNAs) are sequentially processed by two RNase III enzymes, Drosha and Dicer. miR-451 is the only known miRNA whose processing bypasses Dicer and instead relies on the slicer activity of Argonaute-2 (Ago2). miR-451 is highly conserved in vertebrates and regulates erythrocyte maturation, where it becomes the most abundant miRNA. However, the basis for the non-canonical biogenesis of miR-451 is unclear. Here, we show that Ago2 is less efficient than Dicer in processing pre-miRNAs, but this deficit is overcome when miR-144 represses Dicer in a negative-feedback loop during erythropoiesis. Loss of miR-144-mediated Dicer repression in zebrafish embryos and human cells leads to increased canonical miRNA production and impaired miR-451 maturation. Overexpression of Ago2 rescues some of the defects of miR-451 processing. Thus, the evolution of Ago2-dependent processing allows miR-451 to circumvent the global repression of canonical miRNAs elicited, in part, by the miR-144 targeting of Dicer during erythropoiesis.

Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2.

Human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative pathogen of the COVID-19 pandemic, exerts a massive health and socioeconomic crisis. The virus infects alveolar epithelial type 2 cells (AT2s), leading to lung injury and impaired gas exchange, but the mechanisms driving infection and pathology are unclear. We performed a quantitative phosphoproteomic survey of induced pluripotent stem cell-derived AT2s (iAT2s) infected with SARS-CoV-2 at air-liquid interface (ALI). Time course analysis revealed rapid remodeling of diverse host systems, including signaling, RNA processing, translation, metabolism, nuclear integrity, protein trafficking, and cytoskeletal-microtubule organization, leading to cell cycle arrest, genotoxic stress, and innate immunity. Comparison to analogous data from transformed cell lines revealed respiratory-specific processes hijacked by SARS-CoV-2, highlighting potential novel therapeutic avenues that were validated by a high hit rate in a targeted small molecule screen in our iAT2 ALI system.

Practitioner Review: Assessment and treatment of body dysmorphic disorder in young people.

Body dysmorphic disorder (BDD) is a relatively common and highly impairing mental disorder that is strikingly underdiagnosed and undertreated in Child and Adolescent Mental Health Services (CAMHS). The only clinical guidelines for the management of BDD in youth were published nearly 20 years ago, when empirical knowledge was sparse. Fortunately, there has been a surge in research into BDD over the last 10 years, shedding important insights into the phenomenology, epidemiology, assessment and treatment of the disorder in young people. This review aimed to provide an overview of recent research developments of relevance to clinicians and healthcare policymakers. We summarise key findings regarding the epidemiology of BDD in youth, which indicate that the disorder usually develops during teenage years and affects approximately 2% of adolescents at any one point in time. We provide an overview of aetiological research, highlighting that BDD arises from an interplay between genetic and environmental influences. We then focus on screening and assessment strategies, arguing that these are crucial to promote detection and diagnosis of this under-recognised condition. Additionally, we summarise the recommended treatment approaches for BDD in youth, namely cognitive behaviour therapy with or without selective serotonin reuptake inhibitors. The review concludes by highlighting key knowledge gaps and priorities for future research including, but not limited to, better understanding aetiological factors, long-term consequences and treatment.

Prevalence of functional disorders across Europe: a systematic review and meta-analysis.

Functional Disorders (FD) refer to persistent somatic symptoms caused by changes in the functioning of bodily processes. Previous findings suggest that FD are highly prevalent, but overall prevalence rates for FD in European countries are scarce. Therefore, the aim of the present work was to estimate the point prevalence of FD in adult general populations. PubMed and Web of Science were searched from inception to June 2022. A generalized linear mixed-effects model for statistical aggregation was used for statistical analyses. A standardized quality assessment was performed, and PRISMA guidelines were followed. A total of 136 studies were included and systematically synthesized resulting in 8 FD diagnoses. The large majority of studies was conducted in the Northern Europe, Spain, and Italy. The overall point prevalence for FD was 8.78% (95% CI from 7.61 to 10.10%) across Europe, with the highest overall point prevalence in Norway (17.68%, 95% CI from 9.56 to 30.38%) and the lowest in Denmark (3.68%, 95% CI from 2.08 to 6.43%). Overall point prevalence rates for specific FD diagnoses resulted in 20.27% (95% CI from 16.51 to 24.63%) for chronic pain, 9.08% (95% CI from 7.31 to 11.22%) for irritable bowel syndrome, and 8.45% (95% CI from 5.40 to 12.97%) for chronic widespread pain. FD are highly prevalent across Europe, which is in line with data worldwide. Rates implicate the need to set priorities to ensure adequate diagnosis and care paths to FD patients by care givers and policy makers.

Efficacy and Acceptance of Cognitive Behavioral Therapy in Adults with Chronic Fatigue Syndrome: A Meta-analysis.

BACKGROUND: The systematic aggregation of research on cognitive behavioral therapy (CBT) in chronic fatigue syndrome (CFS) needs an update. Although meta-analyses evaluating interventions typically focus on symptom reduction, they should also consider indicators of treatment acceptability, e.g., drop-out rates. METHODS: Randomized controlled trials (RCTs) investigating CBT in adults with CFS compared to inactive and non-specific control groups were included. First, efficacy was examined, considering fatigue, depression, anxiety, and perceived health. Secondly, drop-out rates through different trial stages were analyzed: Non-completion of all mandatory sessions, drop-out (primary study definition), treatment refusal (non-starters), and average of sessions completed. RESULT: We included 15 RCTs with 2015 participants. CBT was more effective than controls in fatigue (g = -0.52, 95%CI -0.69 to -0.35), perceived health, depression, and anxiety at post-treatment. At long-term follow-up the effects were maintained for fatigue and anxiety. Rates of non-completion (22%, 95%CI 3-71), drop-out (15%, 95%CI 9-25), and treatment refusal (7%, 95%CI 3-15) were relatively low, with a high average proportion of sessions completed. Total time of therapy moderated the effect on fatigue, while the number of sessions moderated the effect on perceived health. Fatigue severity influenced adherence. CONCLUSION: The results indicate that CBT for CFS is effective in reducing fatigue, fatigue related impairment, and severity of depression and anxiety. Conclusions on efficacy at follow-ups are still limited. However, adherence is high in CBT. The results may help to inform clinical practice. Future research should focus on examining the maintenance of effects, while also emphasizing the importance of treatment acceptance.

"Too Many Jobs and Not Enough Hands": Immigrant and Refugee Community Health Workers at the Frontlines of the COVID-19 Pandemic.

Refugees and immigrants have experienced heightened health inequities related to COVID-19. As community-embedded frontline health personnel, refugee and immigrant community health workers (riCHWs) played essential roles in the provision of informational, instrumental, and emotional support during the unprecedented first year of the pandemic. Despite the importance of this workforce, riCHWs are at high risk for burnout due to low recognition and demanding workloads. This was exacerbated as riCHWs navigated a new and uncertain health delivery landscape. We sought to glean insight into riCHWs' stressors, coping strategies and resources, and self-efficacy to identify ways to support their work and wellbeing. Using a narrative inquiry approach, we conducted semi-structured, in-depth interviews with 11 riCHWs working in a midsized city in the midwestern United States. We generated three distinct yet interrelated themes: (1) Rapid and trustworthy information is key, (2) Creativity and perseverance are good … structural support is better, and (3) Integrating riCHW expertise into health promotion programming and decision-making. Although riCHWs were deeply committed to enhancing community wellbeing, quickly shifting responsibilities in tandem with structural-level health inequities diminished their self-efficacy and mental health. riCHWs relied on work-based friends/colleagues for informational and emotional support to enhance their capacity to deliver services. Findings suggest increasing opportunities for peer support and idea-exchange, professional development, and integration of riCHW expertise in health promotion decision-making are effective strategies to enhance riCHWs' professional self-efficacy and personal wellbeing.

Enhancing self-esteem in adults with body dysmorphic symptoms: experimental testing and initial evaluation of a brief internet-based training.

BACKGROUND: Low self-esteem is an important factor associated with body dysmorphic concerns. In treatment, self-esteem cannot always be adequately addressed. Internet-based interventions offer a low-threshold and cost-efficient possibility for treating body dysmorphic disorder (BDD). AIMS: For this reason, we conducted two studies to explore the effectiveness of an internet-based intervention targeting improving self-esteem in adults with BDD symptoms. METHOD: The first study investigated the differential effects of a 1-week self-esteem training compared with a 1-week attention-focus training. Two hundred twenty adults with elevated body dysmorphic symptoms were randomly assigned to one of the two trainings. Our second study (n = 58 adults with body dysmorphic symptoms) evaluated an extended 2-week stand-alone self-esteem training. RESULTS: In the first study, self-esteem in different domains (appearance, performance and social), self-focused attention, and BDD symptom severity improved in both groups. Other-focused attention only increased in the attention training group. Participants' overall adherence was high. In the second study we observed significant improvements in self-esteem, BDD symptom severity, and other secondary outcomes, with additional improvements in most outcomes in the second week. Adherence was again high. CONCLUSIONS: Together, these findings show that a brief internet-based intervention may be a highly accepted and effective way of improving self-esteem in people suffering from BDD symptoms.

Impact of obesity on chemotherapy dosing of carboplatin and survival of women with ovarian cancer.

BACKGROUND: The study objective is to examine the impact of obesity on frontline carboplatin dosing in the neoadjuvant and adjuvant settings and to evaluate the association of dosing with survival among epithelial ovarian cancer (EOC) patients. METHODS: We selected 1527 women diagnosed with EOC from January 1, 2011 to October 20, 2021 from a nationwide electronic health record-derived de-identified database. The dose reduction of frontline carboplatin was defined as a relative dose intensity (RDI) < 0.85. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of RDI with survival overall and by histology. RESULTS: Women with a BMI ≥ 30 kg/m2 versus <30 kg/m2 were more likely to be underdosed (RDI < 0.85) with frontline carboplatin. Underdosing of carboplatin in the neoadjuvant setting was associated with worse survival among women with serous tumours (HR = 1.98, 95% CI = 1.15, 3.42). Underdosing of carboplatin in the adjuvant setting was not associated with survival. DISCUSSION: In the real-world setting, underdosing of carboplatin in the neoadjuvant setting was associated with inferior survival among women with serous tumours. With the increasing utilisation of neoadjuvant chemotherapy in EOC, actual weight-based dosing of carboplatin may be important to improve outcomes in this patient population.

Anti-4-1BB immunotherapy enhances systemic immune effects of radiotherapy to induce B and T cell-dependent anti-tumor immune activation and improve tumor control at unirradiated sites.

Radiation therapy (RT) can prime and boost systemic anti-tumor effects via STING activation, resulting in enhanced tumor antigen presentation and antigen recognition by T cells. It is increasingly recognized that optimal anti-tumor immune responses benefit from coordinated cellular (T cell) and humoral (B cell) responses. However, the nature and functional relevance of the RT-induced immune response are controversial, beyond STING signaling, and agonistic interventions are lacking. Here, we show that B and CD4+ T cell accumulation at tumor beds in response to RT precedes the arrival of CD8+ T cells, and both cell types are absolutely required for abrogated tumor growth in non-irradiated tumors. Further, RT induces increased expression of 4-1BB (CD137) in both T and B cells; both in preclinical models and in a cohort of patients with small cell lung cancer treated with thoracic RT. Accordingly, the combination of RT and anti-41BB therapy leads to increased immune cell infiltration in the tumor microenvironment and significant abscopal effects. Thus, 4-1BB therapy enhances radiation-induced tumor-specific immune responses via coordinated B and T cell responses, thereby preventing malignant progression at unirradiated tumor sites. These findings provide a rationale for combining RT and 4-1bb therapy in future clinical trials.

Efficacy of Heart Rate Variability Biofeedback for Somatic Symptom Disorder: A Pilot Randomized Controlled Trial.

OBJECTIVE: Patients with somatic symptom disorder (SSD) often receive targeted intervention only after a long duration of illness. Moreover, the reported effect sizes of interventions for SSD are small. Therefore, improvement and evaluation of interventions are needed. Preliminary evidence suggests autonomic imbalance, for example, lower heart rate variability (HRV) in SSD. HRV biofeedback (HRV-BF) as a method for self-regulation shows initial positive effects in chronic pain and functional syndromes. The aim of this study was to evaluate the efficacy of a brief HRV-BF intervention for SSD. METHODS: Of a total of 50 participants with SSD ( Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ) who were recruited and randomly assigned to four sessions of HRV-BF ( n = 25) or autogenic training (AT; n = 25), 49 participants were analyzed (female, 77.6%; mean [standard deviation] age = 45.3 [14.4] years). The primary outcomes were somatic symptom severity (Screening for Somatoform Disorders, numeric rating scale) and HRV. Secondary outcomes were psychological characteristics of SSD (e.g., the Somatic Symptom Disorder 12 scale, health concerns, emotion regulation). The data were collected before and after intervention and were analyzed with repeated-measures analyses of variance and post hoc t tests. RESULTS: Symptom severity improved after both, HRV-BF and AT. Standard Deviation of the NN Interval and psychological symptoms improved significantly more strongly in the HRV-BF than in the AT group (e.g., Standard Deviation of the NN Interval: ηp2 interaction = 0.10, p = .047). CONCLUSIONS: The improvements in somatic symptoms, but specifically in cognitive-affective symptoms and autonomic regulation, suggest that HRV-BF with only four sessions is a potentially useful intervention option for SSD. Thus, adding this short HRV-BF intervention to existing psychological treatments for SSD may be promising.Trial Registration : German Clinical Trial Register identifier DRKS00017099 ( https://www.drks.de ).

Effect of Anionic Lipids on Mammalian Plasma Cell Membrane Properties.

The effect of lipid composition on models of the inner leaflet of mammalian cell membranes has been investigated. Grazing incidence X-ray diffraction and X-ray and neutron reflectivity have been used to characterize lipid packing and solvation, while electrochemical and infrared spectroscopic methods have been employed to probe phase behavior in an applied electric field. Introducing a small quantity of the anionic lipid dimyristoylphosphatidylserine (DMPS) into bilayers of zwitterionic dimyristoylphosphatidylethanolamine (DMPE) results in a significant change in the bilayer response to an applied field: the tilt of the hydrocarbon chains increases before returning to the original tilt angle on detachment of the bilayer. Equimolar mixtures, with slightly closer chain packing, exhibit a similar but weaker response. The latter also tend to incorporate more solvent during this electrochemical phase transition, at levels similar to those of pure DMPS. Reflectivity measurements reveal greater solvation of lipid layers for DMPS > 30 mol %, matching the greater propensity for DMPS-rich bilayers to incorporate water. Taken together, the data indicate that the range of 10-35 mol % DMPS provides optimum bilayer properties (in flexibility and function as a barrier), which may explain why the DMPS content of cell membranes tends to be found within this range.

Actionable spontaneous antibody responses antagonize malignant progression in ovarian carcinoma.

OBJECTIVE: To demonstrate that shared antibody responses in endometriosis and endometriosis-associated ovarian cancer spontaneously antagonize malignant progression and can be leveraged to develop future immunotherapies. METHODS: B cells from cyopreserved clear cell ovarian carcinoma (CCC, n = 2), endometrioid ovarian carcinoma (EC, n = 2), and endometriomas (n = 2) were isolated, activated, and EBV-immortalized. Antibodies were purified from B cell supernatants and used for screening arrays containing most of the human proteome. Targets were prioritized based on accessibility (transmembrane or secreted proteins), expression in endometriosis and cancer, and concurrent IgA and IgG responses. We focused on antibodies targeting tumor-promoting syndecan binding protein (SDCBP) to demonstrate anti-tumor activity. Immunoblots and qPCR were performed to assess SDCBP expression in ovarian cancer and endometriosis cell lines and tumor samples. Recombinant IgG4 was generated using the variable heavy and light chains of dominant B cell receptors (BCRs) reacting against the extracellular domain of SDCBP, and used in in vivo studies in human CCC- and high-grade serous ovarian carcinoma (HGSOC)-bearing immunodeficient mice. RESULTS: Nine accessible proteins detected by both IgA and IgG were identified in all samples - including SDCBP, which is expressed in ovarian carcinomas of multiple histologies. Administration of α-SDCBP IgG4 in OVCAR3 (HGSOC), TOV21G and RMG-I (CCC) tumor-bearing mice significantly decreased tumor volume compared to control irrelevant IgG4. CONCLUSIONS: Spontaneous antibody responses exert suboptimal but measurable immune pressure against malignant progression in ovarian carcinomas. Using tumor-derived antibodies for developing novel immunotherapeutics warrants further investigation.

Internet-Based Treatment of Body Dysmorphic Disorder: Feasibility, Evaluation, and Self-Report Data.

ABSTRACT: Initial findings indicate the effectiveness of internet-based interventions for body dysmorphic disorder (BDD). In order to substantiate these findings, a seven-module guided internet-based intervention was created and examined. We report the mixed data of participants with clinical and subclinical BDD of the treatment group (n = 18). We investigated the feasibility, the quality of the program content, the design and usability, and its effects on symptom severity and related psychopathology. Adherence to the intervention was low and dropout rate high (55.6%). The program content, perceived website usability, and visual aesthetic were rated high. Credibility and expectancy were on a medium level. Satisfaction with appearance improved significantly in the intention-to-treat analysis (d = 0.58). In sum, symptom-related outcomes and program evaluation showed a positive trend albeit the study conduction was difficult. Future programs should investigate the role of additional motivation strategies and more flexible support addressing the known treatment barriers.

SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing.

RNA provides the framework for the assembly of some of the most intricate macromolecular complexes within the cell, including the spliceosome and the mature ribosome. The assembly of these complexes relies on the coordinated association of RNA with hundreds of trans-acting protein factors. While some of these trans-acting factors are RNA-binding proteins (RBPs), others are adaptor proteins, and others still, function as both. Defects in the assembly of these complexes results in a number of human pathologies including neurodegeneration and cancer. Here, we demonstrate that Silencing Defective 2 (SDE2) is both an RNA binding protein and also a trans-acting adaptor protein that functions to regulate RNA splicing and ribosome biogenesis. SDE2 depletion leads to widespread changes in alternative splicing, defects in ribosome biogenesis and ultimately complete loss of cell viability. Our data highlight SDE2 as a previously uncharacterized essential gene required for the assembly and maturation of the complexes that carry out two of the most fundamental processes in mammalian cells.

Heart Rate Variability, Autonomic Reactivity, and Emotion Regulation during Sadness Induction in Somatic Symptom Disorder.

BACKGROUND: Preliminary evidence suggests altered heart rate variability (HRV) and impaired emotion regulation (ER) in somatic symptom disorder (SSD). Moreover, HRV can be considered an index of ER. Yet, to date, research on HRV and emotional reactivity in SSD is scarce and findings are inconsistent. Thus, this study aimed to examine ER differences, HRV at rest, and in response to emotion induction in persons with SSD compared to controls. METHODS: The sample comprised 44 persons with SSD (DSM-5; 79.5% female, Mage = 45.7, SD = 14.7) and 41 persons without SSD (non-SSD; 78% female, Mage = 44.2, SD = 14.7). We assessed the participants' somatic symptom severity, ER, and control variables (e.g., depressive symptoms). Frequency and time domain HRV by ECG and subjective emotional states were measured at rest, under sadness induction, and during recovery periods. We evaluated baseline between-group differences with t-tests, and HRV and emotional reactivity and recovery with repeated measures ANOVAs. RESULTS: We found no significant differences in resting state HRV between persons with and without SSD. Regarding reactivity and recovery, SSD group showed lower reactivity in SDNN (standard deviation of NN interval) than non-SSD group. Moreover, SSD group reported more maladaptive ER techniques (e.g. rumination) and a higher effort to regulate their emotions during the experiment than non-SSD group. CONCLUSIONS: The study indicated impaired ER in persons with SSD. This finding showed more clearly in self-report than in HRV. Further research on HRV reactivity including tasks evoking other negative emotions in persons with SSD is required.

Empathy, working alliance, treatment expectancy and credibility in video and face-to-face psychotherapeutic first contact.

OBJECTIVE: Video-based therapy has been used increasingly since the onset of the COVID-19 pandemic. Yet, video-based initial psychotherapeutic contact can be problematic due to the limitations of computer-mediated communication. At present, little is known about the effects of video first contact on important psychotherapeutic processes. METHOD: Forty-three individuals (nvideo = 18, nface-to-face = 25) were recruited via an outpatient clinic waiting list and were randomly assigned to video or face-to-face initial psychotherapeutic sessions. Participants rated treatment expectancy before and after the session, and the therapist's empathy, working alliance, and credibility after the session and several days later. RESULTS: Empathy and working alliance ratings of patients and therapists were high and did not differ between the two communication conditions after the appointment or at follow-up. Treatment expectancy increased to a similar extent for the video and face-to-face modalities from pre to post. Willingness to continue with video-based therapy increased in participants who had video contact, but not in those with face-to-face contact. CONCLUSION: This study indicates that crucial processes related to the therapeutic relationship can be initiated via video, without prior face-to-face contact. Given the limited nonverbal communication cues in video appointments, it remains unclear as to how such processes evolve. TRIAL REGISTRATION: German Clinical Trials Register identifier: DRKS00031262..

Tissue losses and metabolic adaptations both contribute to the reduction in resting metabolic rate following weight loss.

OBJECTIVE: To characterize the contributions of the loss of energy-expending tissues and metabolic adaptations to the reduction in resting metabolic rate (RMR) following weight loss. METHODS: A secondary analysis was conducted on data from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy study. Changes in RMR, body composition, and metabolic hormones were examined over 12 months of calorie restriction in 109 individuals. The contribution of tissue losses to the decline in RMR was determined by weighing changes in the size of energy-expending tissues and organs (skeletal muscle, adipose tissue, bone, brain, inner organs, residual mass) assessed by dual-energy X-ray absorptiometry with their tissue-specific metabolic rates. Metabolic adaptations were quantified as the remaining reduction in RMR. RESULTS: RMR was reduced by 101 ± 12 kcal/d as participants lost 7.3 ± 0.2 kg (both p < 0.001). On average, 60% of the total reduction in RMR were explained by energy-expending tissues losses, while 40% were attributed to metabolic adaptations. The loss of skeletal muscle mass (1.0 ± 0.7 kg) was not significantly related to RMR changes (r = 0.14, p = 0.16), whereas adipose tissue losses (7.2 ± 3.0 kg) were positively associated with the reduction in RMR (r = 0.42, p < 0.001) and metabolic adaptations (r = 0.31, p < 0.001). Metabolic adaptations were correlated with declines in leptin (r = 0.27, p < 0.01), triiodothyronine (r = 0.19, p < 0.05), and insulin (r = 0.25, p < 0.05). CONCLUSIONS: During weight loss, tissue loss and metabolic adaptations both contribute to the reduction in RMR, albeit variably. Contrary to popularly belief, it is not skeletal muscle, but rather adipose tissue losses that seem to drive RMR reductions following weight loss. Future research should target personalized strategies addressing the predominant cause of RMR reduction for weight maintenance.

Early Psychological Interventions for Somatic Symptom Disorder and Functional Somatic Syndromes: A Systematic Review and Meta-Analysis.

OBJECTIVE: Psychological treatments for somatic symptom disorder and functional somatic syndromes (SSD/FSS) achieve moderate effects only, potentially because of the high chronicity in these patients. Therefore, we aimed to evaluate whether early treatment, that is, treatment in populations at risk or with recent onset, improves outcome. METHODS: We conducted a systematic review and meta-analysis of (cluster-)randomized controlled trials evaluating early psychological interventions in the prevention and treatment of SSD/FSS in adults compared with inactive control conditions, standard care, or placebo. Individuals at risk for SSD/FSS, suffering from subthreshold symptoms or new onsets of SSD/FSS, or presenting with SSD/FSS for the first time were included. RESULTS: We identified 30 eligible studies, mostly examining pain-related conditions. Interventions were diverse, ranging from bibliotherapy to cognitive-behavioral therapy. We found positive effects on depression post-treatment (Hedges' g = 0.12 [95% confidence interval = 0.03-0.2], k = 5) as well as on somatic symptom severity (g = 0.25 [0.096-0.41], k = 17) and health care utilization (g = 0.31 [0.18-0.44], k = 3) at follow-up. However, because of a high risk of bias, sensitivity to corrections for meta-bias, and missing outcome data, findings should be interpreted cautiously. CONCLUSIONS: Our review shows that targeting SSD/FSS at an early stage represents a conceptual and practical challenge. Readily accessible interventions addressing transsymptomatic processes of SSD/FSS development and consolidation are highly needed. Future studies are needed to evaluate individuals with diverse symptoms, examine symptom history thoroughly, use placebo controls, and report outcomes completely to determine the efficacy of early psychological interventions for SSD/FSS.PROSPERO Registration:CRD42020140122.