What your patient needs to know about a non-specific symptom pathway referral for suspected cancer.

BACKGROUND: Non-specific symptom (NSS) pathways were implemented in the UK in 2017 to address the needs of patients experiencing symptoms such as weight loss, fatigue, or GP 'gut feeling'. AIM: To explore patients' experiences of NSS pathways, and their potential support needs in terms of understanding and navigating these pathways. METHOD: This study employed ethnographic methods across four NHS trusts in England, including interviews with 28 patients and 28 professionals, patient shadowing, and clinical care observations, to examine NSS pathways for cancer diagnosis. Analysis focused on patient communication and understanding of care. RESULTS: Patients found it hard to understand why they were referred. Only a minority of patients appreciated that multiple organs were being investigated for cancer. Progressing through the pathway was also difficult to understand, particularly around who was making decisions and what would happen next. Investigations often resulted in incidental findings. Patients whose persistent symptoms were not explained were often unsure what to do following discharge. CONCLUSION: The findings resulted in recommended messages for GPs to support patients on referral to NSS pathways, including the nature of the pathway, the team that will be responsible for their care, the multiple organ systems that will potentially be investigated, and what will happen if they don't find a cancer. Without this support, patients' difficulties in comprehending previous investigations and findings could result in delays, overtesting, or inadequately targeted investigations, hindering the effective use of their medical history.

Online acceptance and commitment therapy (iACT) for adults with persistent physical symptoms - 3-month follow-up study of a randomized controlled trial.

OBJECTIVE: Persistent physical symptoms (PPS) represent a major health problem affecting daily functioning. This RCT aimed to examine whether a guided Internet-based treatment based on acceptance and commitment therapy (ACT) provided additional benefits compared to Treatment as Usual (TAU) in reducing somatic complaints and psychological distress in adults with PPS. METHODS: A total of 103 adults with PPS related to indoor environments, chronic fatigue or both conditions were assigned to receive either either a 14-week intervention (video-based case conceptualization + Internet-based ACT) combined with TAU (iACT + TAU; n = 50) or TAU alone (n = 53). Somatic symptoms, depression, anxiety, insomnia, and psychological flexibility were assessed from pre-intervention to a 3-month follow-up. Additionally, the association between changes in psychological flexibility from pre- to post-intervention and changes in symptoms from pre to 3-month follow-up was explored. Analyses were conducted using a multigroup method with full information maximum likelihood estimator. RESULTS: The results revealed a significant interaction effect, indicating reductions in somatic symptoms and symptoms of depression and anxiety with moderate to large between-group effects (d = 0.71-1.09). No significant interaction effect was observed in insomnia and measures of psychological flexibility. CONCLUSION: Internet-based ACT, when combined with Treatment as Usual, demonstrated efficacy for individuals with PPS associated with indoor environments and chronic fatigue. These findings are pertinent for primary healthcare providers, suggesting that the current treatment model could serve as a low-threshold first-line treatment option. THE CLINICAL TRIAL REGISTRATION NUMBER: NCT04532827.

Predictors of somatic symptoms during the COVID-19 pandemic: a national longitudinal survey in Japan.

OBJECTIVES: The COVID-19 pandemic has highlighted the long-term consequences of SARS-CoV-2 infection, termed long COVID. However, in the absence of comparative groups, the differentiation of disease progression remains difficult, as COVID-19 symptoms become indistinguishable from symptoms originating from alternative etiologies. This study aimed to longitudinally investigate the association between COVID-19 exposure and the somatic symptoms in the Japanese general population. DESIGN: This was a longitudinal cohort study with 1-year follow-up. SETTING AND PARTICIPANTS: Longitudinal data from 19 545 individuals who participated in the Japan Society and New Tobacco Internet Survey (JASTIS) 2022 and 2023 were included. In this study, we used data from the 2022 JASTIS as baseline data and the 2023 JASTIS as follow-up data. Based on questionnaire responses, respondents were classified into three categories of exposure to COVID-19. OUTCOME MEASURES: The somatic symptoms were assessed by the Somatic Symptom Scale-8 (SSS-8). Using generalised linear models adjusted for baseline covariates, we calculated the ORs of having very high somatic symptoms assessed by SSS-8, attributable to COVID-19 exposure (no COVID-19 cases as the reference group). RESULTS: Follow-up completers were divided into three groups according to COVID-19 exposure (no COVID-19, n=16 012; COVID-19 without O2 therapy, n=3201; COVID-19 with O2 therapy, n=332). After adjusting for all covariates, COVID-19 cases with O2 therapy had a significant positive association (OR 7.60, 95% CI 5.47 to 10.58) with a very high somatic symptoms burden while other COVID-19 exposure groups did not. Pre-existing physical and psychological conditions were also associated with increased risk of somatic symptoms. CONCLUSION: The findings of our study suggest that the severity of COVID-19 symptoms requiring O2 therapy in the acute phase led to high somatic symptoms. Pre-existing conditions were also associated with a subsequent risk of somatic symptoms.

Measuring persistent somatic symptom related stigmatisation: Development of the Persistent Somatic Symptom Stigma scale for Healthcare Professionals (PSSS-HCP).

OBJECTIVE: Persistent somatic symptoms (PSS) describe recurrent or continuously occurring symptoms such as fatigue, dizziness, or pain that have persisted for at least several months. These include single symptoms such as chronic pain, combinations of symptoms, or functional disorders such as fibromyalgia or irritable bowel syndrome. While stigmatisation by healthcare professionals is regularly reported, there are limited measurement instruments demonstrating content validity. This study develops a new instrument to measure stigmatisation by healthcare professionals, the Persistent Somatic Symptom Stigma scale for Healthcare Professionals (PSSS-HCP). METHODS: Development was an iterative process consisting of research team review, item generation and cognitive interviewing. We generated a longlist of 60 items from previous reviews and qualitative research. We conducted 18 cognitive interviews with healthcare professionals in the United Kingdom (UK). We analysed the relevance, comprehensibility and comprehensiveness of items, including the potential for social desirability bias. RESULTS: After research team consensus and initial feedback, we retained 40 items for cognitive interviewing. After our first round of interviews (n = 11), we removed 20 items, added three items and amended five items. After our second round of interviews (n = 7), we removed four items and amended three items. No major problems with relevance, comprehensibility, comprehensiveness or social desirability were found in remaining items. CONCLUSIONS: The provisional version of the PSSS-HCP contains 19 items across three domains (stereotypes, prejudice, discrimination), demonstrating sufficient content validity. Our next step will be to perform a validation study to finalise item selection and explore the structure of the PSSS-HCP.

Psychological flexibility in somatic symptom and related disorders: A case control study.

A key diagnostic criterion of Somatic Symptom and related Disorders (SSD) comprises significant distress and excessive time-and-energy consuming thoughts, feelings, and behavior pertaining to somatic symptoms. This diagnostic criterion is lacking in central sensitivity syndromes (CSS), such as fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome. This strong emphasis on disturbed psychological processing of somatic symptoms, suggests that psychological flexibility is low in SDD. Psychological flexibility is defined as the ability to approach difficult or challenging internal states (thoughts, emotions, and bodily sensations) in a non-judgmental, mindful way, and being committed to pursue one's values. To clarify the potential significance of psychological flexibility in SSD, we examined its levels in 154 people referred to specialized treatment for SDD, as compared to reference groups from the general population encompassing 597 people with CSS and 1422 people without SSD or CSS (controls). Mean levels of psychological flexibility (adjusted for demographic covariates) were lowest for SSD and highest for controls (F = 154.5, p < 0.001, pη2 = 0.13). Percentages of people with low psychological flexibility (<0.8 SD below the mean of controls) were: SSD 74%, CSS 42%, controls 21%. In SSD, higher psychological flexibility was associated with better mental health (ß = 0.56, p < 0.001), but interaction analysis rejected that psychological flexibility preserved health when having more severe somatic symptoms (ß ≤ 0.08, p ≥ 0.10). The results indicate that lower psychological flexibility is a prevalent problem in SSD that is associated with lower mental health. This suggests that it is worthwhile to take account of psychological flexibility in SSD in screening, monitoring, and therapy.

Anxiety and depression status in patients with idiopathic pulmonary fibrosis and outcomes of nintedanib treatment: an observational study.

BACKGROUND: Anxiety and depression are common comorbidities in idiopathic pulmonary fibrosis (IPF) that impair health-related quality of life. However, there is a lack of studies focusing on the mental disorder of IPF after antifibrotic treatment and their related predictive factors. METHODS: Patients with an initial diagnosis of IPF were enrolled. Data on demographics, lung function, Generalized Anxiety Disorder-7 (GAD-7) Scale, Patient Health Questionnaire 9 (PHQ-9), Patient Health Questionnaire-15 (PHQ-15), and St. George's Respiratory Questionnaire total score(SGRQ-T) were collected. Changes in anxiety, depression, somatic symptoms, and quality of life scores before and after nintedanib treatment were compared, and the related predictive factors were analyzed. RESULTS: A total of 56 patients with a first diagnosis of IPF were enrolled, with 42 and 35 patients suffering from anxiety and depression, respectively. The GAD-7, PHQ-9, PHQ-15, and SGRQ scores were higher in the anxiety and depression groups. SGRQ total score (SGRQ-T) [OR = 1.075, 95%CI= (1.011, 1.142)] was an independent predictor of IPF combined with anxiety (p < 0.05); SGRQ-T [OR = 1.080, 95%CI= (1.001, 1.167)] was also an independent predictor of IPF combined with depression (p < 0.05). After treatment, GAD-7, PHQ-9, PHQ-15, and SGRQ scores decreased (p < 0.05). ΔSGRQ-T significantly affected ΔGAD-7 (ß = 0.376, p = 0.009) and ΔPHQ-9 (ß = 0.329, p = 0.022). CONCLUSION: Anxiety and depression in IPF patients are closely related to somatic symptoms, pulmonary function, and quality of life. The SGRQ-T score is of great value for assessing anxiety and depression in patients with IPF. Short-term treatment with nintedanib antifibrotic therapy can alleviate anxiety and depression in IPF patients.

Medically unexplained symptoms are common in women in tertiary neurological healthcare center: A survey cohort study of persons investigated for suspected multiple sclerosis.

BACKGROUND: A significant proportion of individuals with suspicious onset of multiple sclerosis (MS) does not fulfill the diagnostic criteria. Although some receive other diagnoses, many remain undiagnosed and lack healthcare follow-up. This study aimed to characterize persons with undetermined diagnosis (PwUD) through a questionnaire. METHODS: Incident cases with suspected MS were consecutively admitted to a tertiary neurological healthcare center in a prospective cohort study. Those who remained undiagnosed after 40 months (mean, range 31-52) were considered PwUD. They completed a modified questionnaire, previously used in a population-based case-control study of incident MS cases. Their responses were compared with two control cohorts, persons with MS (PwMS) and healthy controls, randomly selected from national registries, matched by age, gender, and area of residence. RESULTS: Out of 271 patients with suspected MS onset, 72 (20.3%) were PwUD with a female majority (79%). The response rate was 83% and 39% reported persisting MS-like symptoms. Compared to controls (n = 548) and PwMS (n = 277), fewer PwUD were currently smoking (p = .4 and p = .03), consumed less alcohol (p = .04 and p = .01), and had children (p = .02 and p = .002). PwUD reported occurrence of other autoimmune disease in 29%, higher compared to PwMS and controls (p < .001 and p < .001). CONCLUSIONS: UD is common among persons investigated for suspected MS, in particular among female parents. Our data suggest that PwUD can be characterized as nonsmokers with low alcohol consumption and a higher prevalence of autoimmune disease, in particular thyroid disease.

Examining the validity and reliability of the Arabic translated version of the depression and somatic symptoms scale (A-DSSS) among the Lebanese adults.

The prevalence of depression is high worldwide, and somatic symptoms are known to be one of the most debilitating aspects of depression. However, clinicians often face challenges in accurately assessing this comorbidity. To address this issue, the Depression and Somatic Symptoms Scale (DSSS) was developed as a self-administered scale that can diagnose both depression and somatic symptoms. The objective of this study is to evaluate the validity and reliability of the Arabic-translated version of the DSSS (A-DSSS) in a sample of Lebanese adults, as well as to explore its associated factors. A cross-sectional study was conducted over a period of one month, from February to March 2023, and involved a sample of 422 participants who were aged 18 years or older. Participants completed a questionnaire that included various measures, including demographic characteristics, alcohol and smoking habits, physical activity history, as well as two scales: the Patient Health Questionnaire-9 (PHQ9) scale and the A-DSSS scale. The A-DSSS showed high internal consistency (Cronbach's alpha = 0.936), strong test-retest reliability (ICC of 0.988 with CI 0.976-0.994; p < 0.001), and a three-factor structure consistent with previous research. Convergent validity was supported by a significant correlation with the PHQ-9. Stepwise linear regression revealed that engaging in physical activity and increasing calorie consumption (as measured by MET-min/week score) were associated with a significant decrease in the A-DSSS total score and subscales. However, a significant increase in the A-DSSS total score was seen in the female gender in comparison for male gender. The A-DSSS revealed good psychometric properties and may be a useful tool for assessing depression and somatic symptoms in this population. The study also identified potential factors associated with depression and somatic symptoms, such as physical activity, calorie consumption, and gender, which may have implications in addressing depression and somatic symptoms for future interventions and clinical practice.

Applying the Somatic Symptom Disorder Diagnosis to Individuals with Fibromyalgia: Strengths and Limitations.

Amidst broad changes to the somatic disorder diagnoses, DSM-IV pain disorder was absorbed into DSM-5's somatic symptom disorder (SSD) as a specifier. However, clinical research testing of its use for the chronic pain population has been limited and its utility remains inconclusive. Using the exemplar of fibromyalgia, this article evaluates the validity, reliability, clinical utility, and acceptability of the SSD pain specifier. The diagnosis appears to have moderate validity but low specificity for the fibromyalgia population. The pain specifier has neither undergone sufficient field testing nor been evaluated for use by medical providers, with available data suggesting low reliability. Further research is needed to establish clinical utility via assessment of differential treatment outcomes. Concerns about social, legal, and economic consequences of classifying pain patients with a mental health diagnosis are outstanding. The current SSD criteria should be used with caution among the fibromyalgia patient population until its application for chronic pain has been further researched.

Pregnancy related factors and temporomandibular disorders evaluated through the diagnostic criteria for temporomandibular disorders (DC/TMD) axis II: a cross sectional study.

INTRODUCTION: Temporomandibular disorder (TMD) is a multifaceted condition impacting the chewing system, with its frequency varying across different age groups and showing a higher incidence in women. The involvement of estrogen in TMD has been examined due to the presence of estrogen receptors in the TMJ area. However, the exact effect of estrogen on TMD is complex. During pregnancy, marked by significant hormonal fluctuations, the impact on TMD has been hypothesized but remains unclear due to inconsistent results from various studies. METHODS: In this cross-sectional study, we enrolled 32 pregnant women consecutively. We gathered information on demographics, TMD evaluations (using the Graded Chronic Pain Scale, Jaw Functional Limitation Scale-20, and Oral Behaviors Checklist), and mental health assessments (including Patient Health Questionnaire-9, Patient Health Questionnaire-15, and Generalized Anxiety Disorder-7). We employed descriptive statistics to summarize continuous and categorical data and used t-tests and chi-square tests for comparisons. We also conducted multivariate linear regression, adjusted for demographic factors, to investigate correlations. RESULTS: The study group mainly consisted of women aged 30-35 (40.6%) and 25-30 (18.8%). Most participants had completed high school (50%) and were married (71.9%). A notable association was found between younger women (under 30) and higher levels of somatic symptoms (p = 0.008) and generalized anxiety (p = 0.015). Women in their second trimester showed lower severity of somatic symptoms (p = 0.04). A significant link was also observed between depression severity and somatic symptom severity (p = 0.01). However, we found no significant correlations with other TMD-related health aspects. DISCUSSION: Our study identified significant associations between psychosomatic and psychological symptoms with variables like age and pregnancy trimester in pregnant women. However, it notably failed to establish a clear relationship between pregnancy-related factors and the severity of temporomandibular disorders (TMD). More comprehensive studies with larger participant pools are necessary to further validate and expand these findings.

Affective dysfunction mediates the link between neuroimmune markers and the default mode network functional connectivity, and the somatic symptoms in somatic symptom disorder.

OBJECTIVE: Somatic symptom disorder (SSD) is characterized by physical symptoms and associated functional impairments that are often comorbid with depression and anxiety disorders. In this study, we explored relationships between affective symptoms and the functional connectivity of the default mode network (DMN) in SSD patients, as well as the impact of peripheral inflammation. We employed mediation analyses to investigate the potential pathways between these factors. METHODS: We recruited a total of 119 individuals (74 unmedicated SSD patients and 45 healthy controls), who were subjected to comprehensive psychiatric and clinical evaluations, blood tests, and resting-state functional magnetic resonance imaging scanning. We assessed neuroimmune markers (interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), tryptophan, serotonin, and 5-hydroxyindoleacetic acid (5-HIAA)), clinical indicators of somatic symptoms, depression, anxiety, anger, alexithymia, and functional connectivity (FC) within the DMN regions. Data were analyzed using correlation and mediation analysis, with a focus on exploring potential relations between clinical symptoms, blood indices, and DMN FCs. RESULTS: Patients with SSD had higher clinical scores as well as IL-6 and TNF-α levels compared with those in the control group (P < 0.05). The SSD group exhibited lower FC strength between the left inferior parietal lobule and left prefrontal cortex (Pfalse discovery rate (FDR) < 0.05). Exploratory correlation analysis revealed that somatic symptom scores were positively correlated with affective symptom scores, negatively correlated with the FC strength between the intra prefrontal cortex regions, and correlated with levels of IL-6, TNF- α, and tryptophan (uncorrected P < 0.01). Mediation analysis showed that levels of anxiety and trait anger significantly mediated the relations between DMN FC strength and somatic symptoms. In addition, the DMN FC mediated the level of trait anger with respect to somatic symptoms (all PFDR < 0.05). The levels of depression and trait anger exhibited significant mediating effects as suppressors of the relations between the level of 5-HIAA and somatic symptom score (all PFDR < 0.05). Further, the level of 5-HIAA had a mediating effect as a suppressor on the relation between DMN FC and state anger. Meanwhile, the levels of hs-CRP and IL-6 had full mediating effects as suppressors when explaining the relations of DMN FC strengths with the level of depression (all PFDR < 0.05). The patterns of valid mediation pathways were different in the control group. CONCLUSIONS: Affective symptoms may indirectly mediate the associations between DMN connectivity, somatic symptoms, and neuroimmune markers. Inflammatory markers may also mediate the impact of DMN connectivity on affective symptoms. These results emphasize the importance of affective dysregulation in understanding the mechanisms of SSD and have potential implications for the development of tailored therapeutic approaches for SSD patients with affective symptoms. Furthermore, in SSD research using DMN FC or neuroimmune markers, considering and incorporating such mediating effects of affective symptoms suggests the possibility of more accurate prediction and explanation.

A pontomesencephalic PACAPergic pathway underlying panic-like behavioral and somatic symptoms in mice.

Panic disorder is characterized by uncontrollable fear accompanied by somatic symptoms that distinguish it from other anxiety disorders. Neural mechanisms underlying these unique symptoms are not completely understood. Here, we report that the pituitary adenylate cyclase-activating polypeptide (PACAP)-expressing neurons in the lateral parabrachial nucleus projecting to the dorsal raphe are crucial for panic-like behavioral and physiological alterations. These neurons are activated by panicogenic stimuli but inhibited in conditioned fear and anxiogenic conditions. Activating these neurons elicits strong defensive behaviors and rapid cardiorespiratory increase without creating aversive memory, whereas inhibiting them attenuates panic-associated symptoms. Chemogenetic or pharmacological inhibition of downstream PACAP receptor-expressing dorsal raphe neurons abolishes panic-like symptoms. The pontomesencephalic PACAPergic pathway is therefore a likely mediator of panicogenesis, and may be a promising therapeutic target for treating panic disorder.

Exploratory study of cold hypersensitivity in Japanese women: genetic associations and somatic symptom burden.

Temperature perception is essential for humans to discern the environment and maintain homeostasis. However, some individuals experience cold hypersensitivity, characterized by a subjective feeling of coldness despite ambient environmental temperatures being normal, the underlying mechanisms of which are unknown. In this study, we aimed to investigate the relationship between subjective cold symptoms and somatic burden or single nucleotide polymorphisms to understand the causes of cold hypersensitivity. We conducted an online questionnaire survey [comprising 30 questions, including past medical history, subjective symptoms of cold hypersensitivity, and the Somatic Symptom Scale-8 (SSS-8)]. Respondents were 1200 Japanese adult female volunteers (age: 20-59 years), recruited between April 21 and May 25, 2022, who were customers of MYCODE, a personal genome service in Japan. Among the 1111 participants, 599 (54%) reported cold hypersensitivity. Higher cold hypersensitivity severity was positively associated with the SSS-8 scores. Additionally, a genome-wide association study for cold hypersensitivity was conducted using array-based genomic data obtained from genetic testing. We identified 11 lead variants showing suggestive associations (P < 1 × 10-5) with cold hypersensitivity, some of which showed a reasonable change in expression in specific tissues in the Genotype-Tissue Expression database. The study findings shed light on the underlying causes of cold hypersensitivity.

Clinical outcomes, medical costs, and medication usage patterns of different somatic symptom disorders and functional somatic syndromes: a population-based study in Taiwan.

BACKGROUND: Somatic symptom disorders (SSD) and functional somatic syndromes (FSS) are often regarded as similar diagnostic constructs; however, whether they exhibit similar clinical outcomes, medical costs, and medication usage patterns has not been examined in nationwide data. Therefore, this study focused on analyzing SSD and four types of FSS (fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, functional dyspepsia). METHODS: This population-based matched cohort study utilized Taiwan's National Health Insurance (NHI) claims database to investigate the impact of SSD/FSS. The study included 2 615 477 newly diagnosed patients with SSD/FSS and matched comparisons from the NHI beneficiary registry. Healthcare utilization, mortality, medical expenditure, and medication usage were assessed as outcome measures. Statistical analysis involved Cox regression models for hazard ratios, generalized linear models for comparing differences, and adjustment for covariates. RESULTS: All SSD/FSS showed significantly higher adjusted hazard ratios for psychiatric hospitalization and all-cause hospitalization compared to the control group. All SSD/FSS exhibited significantly higher adjusted hazard ratios for suicide, and SSD was particularly high. All-cause mortality was significantly higher in all SSD/FSS. Medical costs were significantly higher for all SSD/FSS compared to controls. The usage duration of all psychiatric medications and analgesics was significantly higher in SSD/FSS compared to the control group. CONCLUSION: All SSD/FSS shared similar clinical outcomes and medical costs. The high hazard ratio for suicide in SSD deserves clinical attention.

Anxiety Sensitivity and Distress Tolerance in Relation to Smoking Abstinence Expectancies Among Black Individuals Who Smoke.

OBJECTIVE: Black individuals who smoke in the United States experience significant tobacco-related disparities. Although prior work has established that smoking abstinence expectancies play an important role in smoking-related outcomes, few studies have examined potential individual difference factors that may be relevant to smoking abstinence expectancies among Black individuals who smoke. The present study investigated anxiety sensitivity and distress tolerance in relation to smoking abstinence expectancies among a sample of Black individuals who smoke. METHOD: Participants were 86 Black adults who smoke cigarettes daily (M age = 46.07 years, SD = 10.37; 26.7% female). Four separate linear regression analyses were conducted to evaluate the relation between anxiety sensitivity, distress tolerance, and their interaction with each of the four smoking abstinence expectancies (i.e., somatic symptoms, positive consequences, harmful consequences, and negative mood). RESULTS: Results indicated that higher anxiety sensitivity was related to higher somatic symptoms, harmful consequences, and negative mood abstinence expectancies, whereas distress tolerance was related to higher positive consequences. Further, anxiety sensitivity and distress tolerance interacted to confer greater expectancies for the positive consequences of quitting. CONCLUSIONS: The current findings are among the first to document that anxiety sensitivity and distress tolerance are clinically relevant factors to consider when tailoring smoking cessation treatments for Black individuals who smoke. Future research is needed to examine distress tolerance and anxiety sensitivity as longitudinal predictors of smoking abstinence expectancies among Black individuals who smoke.

Establishment of the Effectiveness of Early Versus Late Stem Cell Gene Therapy in Mucopolysaccharidosis II for Treating Central Versus Peripheral Disease.

Mucopolysaccharidosis type II (MPSII) is a rare pediatric X-linked lysosomal storage disease, caused by heterogeneous mutations in the iduronate-2-sulfatase (IDS) gene, which result in accumulation of heparan sulfate (HS) and dermatan sulfate within cells. This leads to severe skeletal abnormalities, hepatosplenomegaly, and cognitive deterioration. The progressive nature of the disease is a huge obstacle to achieve full neurological correction. Although current therapies can only treat somatic symptoms, a lentivirus-based hematopoietic stem cell gene therapy (HSCGT) approach has recently achieved improved central nervous system (CNS) neuropathology in the MPSII mouse model following transplant at 2 months of age. In this study, we evaluate neuropathology progression in 2-, 4- and 9-month-old MPSII mice, and using the same HSCGT strategy, we investigated somatic and neurological disease attenuation following treatment at 4 months of age. Our results showed gradual accumulation of HS between 2 and 4 months of age, but full manifestation of microgliosis/astrogliosis as early as 2 months. Late HSCGT fully reversed the somatic symptoms, thus achieving the same degree of peripheral correction as early therapy. However, late treatment resulted in slightly decreased efficacy in the CNS, with poorer brain enzymatic activity, together with reduced normalization of HS oversulfation. Overall, our findings confirm significant lysosomal burden and neuropathology in 2-month-old MPSII mice. Peripheral disease is readily reversible by LV.IDS-HSCGT regardless of age of transplant, suggesting a viable treatment for somatic disease. However, in the brain, higher IDS enzyme levels are achievable with early HSCGT treatment, and later transplant seems to be less effective, supporting the view that the earlier patients are diagnosed and treated, the better the therapy outcome.

Changes in depression symptom profile with gender-affirming hormone use in transgender persons.

BACKGROUND: Women show higher prevalence of depression and different symptomatology than men, possibly influenced by sex hormones. Many transgender persons, who face a high risk of depression, use Gender-Affirming Hormone Therapy (GAHT), but the impact of GAHT on depressive symptom profiles is unknown. METHODS: This study examined depressive symptoms in transgender persons before GAHT and after 3- and 12 months of GAHT. We used the Inventory of Depressive Symptomatology-Self Report to assess depressive symptoms, exploratory factor analysis (EFA) to assess symptom clusters, and linear mixed models to assess changes in symptom clusters. RESULTS: This study included 110 transmasculine (TM) and 89 transfeminine (TF) participants. EFA revealed four symptom clusters: mood, anxiety, lethargy, and somatic symptoms. Changes in total depressive symptoms significantly differed between TM and TF groups. After 3 months of GAHT, TM participants reported improvement in lethargy (-16 %; 95%CI: -29 %; -2 %), and after 12 months TF participants reported worsening in low mood (24 %; 95%CI: 3 %; 51 %), but absolute score changes were modest. Neither group showed changes in anxiety or somatic symptoms. LIMITATIONS: This study had limited sample sizes at 12 months follow-up and did not include relevant biological or psychosocial covariates. DISCUSSION: Changes in depressive symptoms after GAHT use differ in TM and TF persons: TM persons report slight improvements in lethargy, whereas TF persons report a slight increase in low mood. Starting GAHT represents a significant life event with profound social and physical effects, and further research should assess social and biological effects of GAHT on mood-related symptoms.

Somatic symptom severity, depression and anxiety associations with pancreatitis and undifferentiated abdominal pain in surgical inpatients.

BACKGROUND: Somatic Symptom Disorder is a psychiatric diagnosis that describes the experience of physical symptoms and associated distress, that is disproportionate to recognized organic pathology. Somatic symptom severity (SSS) may be associated with some surgical diagnoses; particularly the complex pain associated with pancreatitis, or the diagnostic ambiguity of undifferentiated abdominal pain (UAP). We aimed to estimate the prevalence of SSS in different diagnostic groups in surgical inpatients with abdominal pain; and to estimate the magnitude and direction of any association of SSS, anxiety and depression. METHODS: Cross sectional analysis (n = 465) of adult admissions with non-traumatic abdominal pain, at a tertiary hospital in Australia. We estimated SSS with the Patient Health Questionnaire-15 (PHQ-15), depression with the Patient Health Questionnaire (PHQ-9) and anxiety with the General Anxiety Disorder (GAD-7), at standard cut-points ≥ 10; comparing acute pancreatitis (n = 20), chronic pancreatitis (n = 18) and UAP (n = 64) versus other causes of abdominal pain. RESULTS: Somatic symptoms were common, 52% having moderate and 19.6% severe SSS. There was an association between moderate SSS and pancreatitis (OR 2.11, 95% CI 1.05-4.25) and depressive symptoms and chronic pancreatitis (OR = 3.47, 95% CI 1.31-9.24). There was no significant association between the four mental health categories and UAP. CONCLUSIONS: SSS and psychological comorbidity were common in a surgical inpatients admitted for abdominal pain and equally represented across most diagnostic sub-groups. However, the pancreatitis sub-group had greater proportions with clinically significant SSS and depression, suggesting that they have a higher requirement for psychological assessment and intervention.

The effects of art therapy on quality of life and psychosomatic symptoms in adults with cancer: a systematic review and meta-analysis.

BACKGROUND: Cancer-related psychological and physical disorders can mean stressful and painful experiences for patients. Art therapy, a form of complementary and alternative medicine, is an increasingly popular way to decrease emotional stress, alleviate somatic symptoms, and improve quality of life in patients with cancer. However, current systematic reviews have not explored the beneficial effects of art therapy. Moreover, there have been inconsistent findings on the effect of this therapy, and there is insufficient evidence to confirm the effects in adults with cancer. The objective of this study was to determine the efficacy of art therapy in improving quality of life and psychosomatic symptoms in adults with cancer. METHODS: This systematic review and meta-analysis included adults with all kinds of cancer. Six English-language and three large Chinese-language databases were comprehensively searched for relevant studies. Gray literature and references were also checked. The quality of the included studies was evaluated using the Cochrane risk-of-bias assessment tool. RESULTS: Eight eligible randomized controlled trials conducted in four countries were included. Art therapy improved overall quality of life, but had no significant effect on psychological health or physical health sub-dimensions in women with cancer. Moreover, art therapy alleviated anxiety and depression, but had only a tendency toward an effect on somatic symptoms. CONCLUSIONS: Moderate-quality evidence shows that art therapy is beneficial for women with cancer in terms of improving the overall quality of life and alleviating emotional symptoms (anxiety and depression). However, more high-quality randomized controlled trials are needed to determine the efficacy of this therapy on somatic symptoms.

Functional neurological disorder and functional somatic syndromes among sexual and gender minority people: A scoping review.

OBJECTIVE: To describe the current literature on functional neurological disorder and functional somatic syndromes among sexual and gender minority people (SGM). METHODS: A search string with descriptors of SGM identity and functional disorders was entered into PubMed, Embase, Web of Science, PsycInfo, and CINAHL for articles published before May 24, 2022, yielding 3121 items entered into Covidence, where 835 duplicates were removed. A neurologist and neuropsychiatrist screened titles and abstracts based on predefined criteria, followed by full-text review. A third neurologist adjudicated discrepancies. Eligible publications underwent systematic data extraction and statistical description. RESULTS: Our search identified 26 articles on functional disorders among SGM people. Most articles were case (13/26, 46%) or cross-sectional (4/26, 15%) studies. Gender minority people were represented in 50% of studies. Reported diagnoses included fibromyalgia (n = 8), functional neurological disorder (n = 8), somatic symptom disorder (n = 5), chronic fatigue syndrome (n = 3), irritable bowel syndrome (n = 2), and other functional conditions (n = 3). Three cohort studies of fibromyalgia or somatic symptom disorder reported an overrepresentation of gender minority people compared to cisgender cohorts or general population measures. Approximately half of case studies reported pediatric or adolescent onset (7/13, 54%), functional neurological disorder diagnosis (7/13, 54%), and symptom improvement coinciding with identity-affirming therapeutic interventions (7/13, 58%). CONCLUSION: Despite a methodologically rigorous literature search, there are limited data on functional neurological disorder and functional somatic syndromes among SGM people. Several studies reported increased prevalence of select conditions among transgender people. More observational studies are needed regarding the epidemiology and clinical course of functional disorders among SGM people.