Hemorrhoidal disease and its genetic association with depression, bipolar disorder, anxiety disorders, and schizophrenia: a bidirectional mendelian randomization study.

BACKGROUND: Hemorrhoids and psychiatric disorders exhibit high prevalence rates and a tendency for relapse in epidemiological studies. Despite this, limited research has explored their correlation, and these studies are often subject to reverse causality and residual confounding. We conducted a Mendelian randomization (MR) analysis to comprehensively investigate the association between several mental illnesses and hemorrhoidal disease. METHODS: Genetic associations for four psychiatric disorders and hemorrhoidal disease were obtained from large consortia, the FinnGen study, and the UK Biobank. Genetic variants associated with depression, bipolar disorder, anxiety disorders, schizophrenia, and hemorrhoidal disease at the genome-wide significance level were selected as instrumental variables. Screening for potential confounders in genetic instrumental variables using PhenoScanner V2. Bidirectional MR estimates were employed to assess the effects of four psychiatric disorders on hemorrhoidal disease. RESULTS: Our analysis revealed a significant association between genetically predicted depression and the risk of hemorrhoidal disease (IVW, OR=1.20,95% CI=1.09 to 1.33, P <0.001). We found no evidence of associations between bipolar disorder, anxiety disorders, schizophrenia, and hemorrhoidal disease. Inverse MR analysis provided evidence for a significant association between genetically predicted hemorrhoidal disease and depression (IVW, OR=1.07,95% CI=1.04 to 1.11, P <0.001). CONCLUSIONS: This study offers MR evidence supporting a bidirectional causal relationship between depression and hemorrhoidal disease.

Risk for diagnosis or treatment of mood or anxiety disorders in adults after SARS-CoV-2 infection, 2020-2022.

COVID-19 is associated with increased risks for mood or anxiety disorders, but it remains uncertain how the association evolves over time or which patient groups are most affected. We conducted a retrospective cohort study using a nationwide database of electronic health records to determine the risk of depressive or anxiety disorder diagnoses after SARS-CoV-2 infection by 3-month blocks from January 2020 to April 2022. The study population comprised 822,756 patients (51.8% female; mean age 42.8 years) with COVID-19 and 2,034,353 patients with other respiratory tract infections (RTIs) (53.5% female, mean age 30.6 years). First time diagnoses of depressive or anxiety disorders 14 days to 3 months after infection, as well as new or new plus recurrent prescriptions of antidepressants or anxiolytics, were compared between propensity score matched cohorts using Kaplan-Meier survival analysis, including hazard ratio (HR) and 95% confidence interval (CI). Risk of a new diagnosis or prescription was also stratified by age, sex, and race to better characterize which groups were most affected. In the first three months of the pandemic, patients infected with SARS-CoV-2 had significantly increased risk of depression or anxiety disorder diagnosis (HR 1.65 [95% CI, 1.30-2.08]). October 2021 to January 2022 (HR, 1.12 [95% CI, 1.06-1.18]) and January to April 2022 (HR, 1.08 [95% CI, 1.01-1.14]). Similar temporal patterns were observed for antidepressant and anxiolytic prescriptions, when the control group was patients with bone fracture, when anxiety and depressive disorders were considered separately, when recurrent depressive disorder was tested, and when the test period was extended to 6 months. COVID-19 patients ≥65 years old demonstrated greatest absolute risk at the start of the pandemic (6.8%), which remained consistently higher throughout the study period (HR, 1.20 [95% CI, 1.13-1.27]), and overall, women with COVID-19 had greater risk than men (HR 1.35 [95% CI 1.30-1.40]).

Association between white matter hyperintensity and anxiety/depression.

Although previous studies have explored the associations of white matter hyperintensity with psychiatric disorders, the sample size is small and the conclusions are inconsistent. The present study aimed to further systematically explore the association in a larger sample. All data were extracted from the UK Biobank. First, general linear regression models and logistic regression models were used to assess the association between white matter hyperintensity volume and anxiety/depression. White matter hyperintensity has been classified into periventricular white matter hyperintensity and deep white matter hyperintensity. Anxiety was determined by General Anxiety Disorder-7 score (n = 17,221) and self-reported anxiety (n = 15,333), depression was determined by Patient Health Questionnaire-9 score (n = 17,175), and self-reported depression (n = 14,519). Moreover, we employed Cox proportional hazard models to explore the association between white matter hyperintensity volume and anxiety/depression. The covariates included in fully adjusted model are age, gender, body mass index, Townsend deprivation index, healthy physical activity, cigarette consumption, alcohol consumption, educational attainment, diabetes, hypertension, and coronary heart disease. The results of the fully adjusted model showed that white matter hyperintensity volume was significantly associated with General Anxiety Disorder-7 score (periventricular white matter hyperintensity: ß = 0.152, deep white matter hyperintensity: ß = 0.094) and Patient Health Questionnaire-9 score (periventricular white matter hyperintensity: ß = 0.168). Logistic regression analysis results indicated that periventricular white matter hyperintensity volume (odds ratio = 1.153) was significantly associated with self-reported anxiety. After applying the Cox proportional hazard models, we found that larger white matter hyperintensity volume was associated with increased risk of depression (periventricular white matter hyperintensity: hazard ratio = 1.589, deep white matter hyperintensity: hazard ratio = 1.200), but not anxiety. In summary, our findings support a positive association between white matter hyperintensity volume and depression.

Maintenance or Discontinuation of Antidepressants in Primary Care.

BACKGROUND: Patients with depression who are treated in primary care practices may receive antidepressants for prolonged periods. Data are limited on the effects of maintaining or discontinuing antidepressant therapy in this setting. METHODS: We conducted a randomized, double-blind trial involving adults who were being treated in 150 general practices in the United Kingdom. All the patients had a history of at least two depressive episodes or had been taking antidepressants for 2 years or longer and felt well enough to consider stopping antidepressants. Patients who had received citalopram, fluoxetine, sertraline, or mirtazapine were randomly assigned in a 1:1 ratio to maintain their current antidepressant therapy (maintenance group) or to taper and discontinue such therapy with the use of matching placebo (discontinuation group). The primary outcome was the first relapse of depression during the 52-week trial period, as evaluated in a time-to-event analysis. Secondary outcomes were depressive and anxiety symptoms, physical and withdrawal symptoms, quality of life, time to stopping an antidepressant or placebo, and global mood ratings. RESULTS: A total of 1466 patients underwent screening. Of these patients, 478 were enrolled in the trial (238 in the maintenance group and 240 in the discontinuation group). The average age of the patients was 54 years; 73% were women. Adherence to the trial assignment was 70% in the maintenance group and 52% in the discontinuation group. By 52 weeks, relapse occurred in 92 of 238 patients (39%) in the maintenance group and in 135 of 240 (56%) in the discontinuation group (hazard ratio, 2.06; 95% confidence interval, 1.56 to 2.70; P<0.001). Secondary outcomes were generally in the same direction as the primary outcome. Patients in the discontinuation group had more symptoms of depression, anxiety, and withdrawal than those in the maintenance group. CONCLUSIONS: Among patients in primary care practices who felt well enough to discontinue antidepressant therapy, those who were assigned to stop their medication had a higher risk of relapse of depression by 52 weeks than those who were assigned to maintain their current therapy. (Funded by the National Institute for Health Research; ANTLER ISRCTN number, ISRCTN15969819.).

Peripheral vertigo and subsequent risk of depression and anxiety disorders: a prospective cohort study using the UK Biobank.

BACKGROUND: Peripheral vertigo is often comorbid with psychiatric disorders. However, no longitudinal study has quantified the association between peripheral vertigo and risk of psychiatric disorders. Furthermore, it remains unknown how the white matter integrity of frontal-limbic network relates to the putative peripheral vertigo-psychiatric disorder link. METHODS: We conducted a cohort study including 452,053 participants of the UK Biobank with a follow-up from 2006 through 2021. We assessed the risks of depression and anxiety disorders in relation to a hospitalization episode involving peripheral vertigo using Cox proportional hazards models. We also examined the associations of peripheral vertigo, depression, and anxiety with MRI fractional anisotropy (FA) in a subsample with brain MRI data (N = 36,087), using multivariable linear regression. RESULTS: Individuals with an inpatient diagnosis of peripheral vertigo had elevated risks of incident depression (hazard ratio (HR) 2.18; 95% confidence interval (CI) 1.79-2.67) and anxiety (HR 2.11; 95% CI 1.71-2.61), compared to others, particularly within 2 years after hospitalization (HR for depression 2.91; 95% CI 2.04-4.15; HR for anxiety 4.92; 95% CI 3.62-6.69). Depression was associated with lower FA in most studied white matter regions, whereas anxiety and peripheral vertigo did not show statistically significant associations with FA. CONCLUSIONS: Individuals with an inpatient diagnosis of peripheral vertigo have increased subsequent risks of depression and anxiety disorders, especially within 2 years after hospitalization. Our findings further indicate a link between depression and lower microstructural connectivity as well as integrity beyond the frontal-limbic network.

Daily routine disruptions and psychiatric symptoms amid COVID-19: a systematic review and meta-analysis of data from 0.9 million individuals in 32 countries.

BACKGROUND: There is currently a deficit of knowledge about how to define, quantify, and measure different aspects of daily routine disruptions amid large-scale disasters like COVID-19, and which psychiatric symptoms were more related to the disruptions. This study aims to conduct a systematic review and meta-analysis on the probable positive associations between daily routine disruptions and mental disorders amid the COVID-19 pandemic and factors that moderated the associations. METHODS: PsycINFO, Web of Science, PubMed, and MEDLINE were systematically searched up to April 2023 (PROSPERO: CRD42023356846). Independent variables included regularity, change in frequency, and change in capability of different daily routines (i.e., physical activity, diet, sleep, social activities, leisure activities, work and studies, home activities, smoking, alcohol, combined multiple routines, unspecified generic routines). Dependent variables included symptoms and/or diagnoses of mental disorders (i.e., depression, anxiety, post-traumatic stress disorder, and general psychological distress). RESULTS: Fifty-three eligible studies (51 independent samples, 910,503 respondents) were conducted in five continents. Daily routine disruptions were positively associated with depressive symptoms (r = 0.13, 95% CI = [0.06; 0.20], p < 0.001), anxiety symptoms (r = 0.12, 95% CI = [0.06; 0.17], p < 0.001), and general psychological distress (r = 0.09, 95% CI = [0.02; 0.16], p = 0.02). The routine-symptom associations were significant for physical activity, eating, sleep, and smoking (i.e., type), routines that were defined and assessed on regularity and change in capability (i.e., definition and assessment), and routines that were not internet-based. While the positive associations remained consistent across different sociodemographics, they were stronger in geo-temporal contexts with greater pandemic severity, lower governmental economic support, and when the routine-symptom link was examined prospectively. CONCLUSIONS: This is one of the first meta-analytic evidence to show the positive association between daily routine disruptions and symptoms of mental disorders among large populations as COVID-19 dynamically unfolded across different geo-temporal contexts. Our findings highlight the priority of behavioral adjustment for enhancing population mental health in future large-scale disasters like COVID-19.

Biopsychosocial Late Effects After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases from Colorectal and Appendiceal Cancer: A National Prospective Cohort Study.

BACKGROUND: Colorectal cancer with peritoneal metastases can be treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Treatment may result in biopsychosocial late effects (LEs). We explored the frequency and severity of the following biopsychosocial LEs: anxiety, depression, fear of cancer recurrence (FCR), insomnia, fatigue, cognitive impairment, and pain, and evaluated their impact on quality of life (QoL). METHOD: This was a national prospective cohort study screening for LEs during the period January 2021-May 2023. Patients completed the following questionnaires: General Anxiety Disorder-7, Patient Health Questionnaire-9, FCR Inventory-Short Form, Insomnia Severity Index, Functional Assessment of Chronic Illness Therapy-Fatigue, cognitive impairment (six items from the European Organisation for Research and Treatment of Cancer Item Library), and the Rectal Cancer Pain Score. Preregistration was completed at ClinicalTrials.gov (NCT04956107). RESULT: In total, 99 patients were included. The mean age was 61 years and 57% were women. At 3 months after surgery, the frequent LEs were fatigue (72%), FCR (58%), and pain (48%), and at 12 months after surgery, the frequent LEs were FCR (65%), fatigue (40%), and insomnia (33%). More than half of the patients (54%) reported at least two LEs after 12 months. Patients with moderate-to-severe LEs reported a lower QoL than patients with no/mild LEs. Patients with no/mild LEs had a similar QoL as the Danish norm population. CONCLUSION: Biopsychosocial LEs were prevalent. The QoL of patients reporting LEs in the worst severity categories was negatively impacted. Screening and treatment for these LEs should be a focus in cancer survivor follow-up.

Early-life participation in cognitively stimulating activities and risk of depression and anxiety in late life.

BACKGROUND: Early-life stressful experiences are associated with increased risk of adverse psychological outcomes in later life. However, much less is known about associations between early-life positive experiences, such as participation in cognitively stimulating activities, and late-life mental health. We investigated whether greater engagement in cognitively stimulating activities in early life is associated with lower risk of depression and anxiety in late life. METHODS: We surveyed former participants of the St. Louis Baby Tooth study, between 22 June 2021 and 25 March 2022 to collect information on participants' current depression/anxiety symptoms and their early-life activities (N = 2187 responded). A composite activity score was created to represent the early-life activity level by averaging the frequency of self-reported participation in common cognitively stimulating activities in participants' early life (age 6, 12, 18), each rated on a 1 (least frequent) to 5 (most frequent) point scale. Depression/anxiety symptoms were measured by Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Screener (GAD-7). We used logistic regressions to estimate odds ratios (OR) and 95% confidence intervals (CI) of outcome risk associated with frequency of early-life activity. RESULTS: Each one-point increase in the early-life composite cognitive activity score was associated with an OR of 0.54 (95% CI 0.38-0.77) for late-life depression and an OR of 0.94 (95% CI 0.61-1.43) for late-life anxiety, adjusting for age, sex, race, parental education, childhood family structure, and socioeconomic status. CONCLUSIONS: More frequent participation in cognitively stimulating activities during early life was associated with reduced risk of late-life depression.

The predictive effect of family genetic risk scores as an indirect measure of causal effects of one disorder on another.

BACKGROUND: One potential cause of comorbidity is the direct causal effect of one disorder - A - on risk for subsequent onset of disorder B. Could genetic risk scores be utilized to test for such an effect? If disorder A causally impacts on risk for disorder B, then genetic risk for disorder A should be lower in cases of disorder A with v. without a prior onset of B. METHODS: In all individuals (n = 905 736) born in Sweden from 1980 to 1990, from six psychiatric and drug use disorders (major depression, anxiety disorders, alcohol use disorder, drug use disorder, bipolar disorder, and schizophrenia), we formed 14 pairs of disorders A and B. In these pairs, we compared, using Cox proportional hazards models, the predictive effect of the familial-genetic risk score (FGRS) for disorder B in those who had v. had not had a prior onset of disorder A. RESULTS: In all pairs, the impact of the FGRS for disorder B was significantly stronger in cases without v. with a prior history of disorder A. These effects were similar across sex, stable across levels of FGRS and not likely due to clinician bias. In many of our disorder pairs, previous clinical studies suggest a mechanism for a causal effect of disorder A on B. CONCLUSIONS: Our findings provide indirect evidence that the occurrence of one psychiatric or substance use disorder often has a causal effect on risk for subsequent disorders. This mechanism may substantially contribute to the widespread comorbidity among psychiatric conditions.

Incidence of anxiety disorder in adults with hidradenitis suppurativa.

BACKGROUND: There are limited data on the risk of new-onset anxiety disorders in patients with hidradenitis suppurativa (HS). OBJECTIVES: To compare the risk of new-onset anxiety disorder in patients with HS and controls, and to describe risk factors for the development of anxiety in patients with HS. METHODS: We carried out a retrospective cohort analysis of a US electronic health records database between 2011 and 2020. Adults newly diagnosed with HS at a dermatology or primary care visit and control participants were included. The primary outcome was a new diagnosis of generalized anxiety disorder, phobic disorders, panic disorder or unspecified anxiety. Cox proportional hazards regression was used to compare the crude risk of any anxiety disorder between groups and to assess the independent association with HS while controlling for potential demographic, clinical and healthcare-related confounders. RESULTS: Among 9597 patients with HS and 959 493 controls, the incidence rate (IR) of anxiety was 5.74 and 3.86 per 100 person-years (PY), respectively. The crude risk among all patients was 48% higher for those with HS vs. controls [hazard ratio (HR) 1.48, 95% confidence interval (CI) 1.40-1.55]. When stratified by index encounter type, patients with HS had 2.43 (95% CI 2.13-2.77) times the risk of anxiety disorder than dermatology controls and 1.46 (95%CI 1.38-1.55) times the risk than primary care controls. The adjusted HR for patients with HS vs. controls was 1.11 (95% CI 1.05-1.17) overall, 1.26 (95% CI 1.07-1.48) in the dermatology subgroup and 1.07 (95% CI 1.01-1.13) in the primary care subgroup. Risk factors for an incident anxiety diagnosis among patients with HS included depression (HR 1.69, 95% CI 1.48-1.93), female sex (HR 1.41, 95% CI 1.23-1.60), younger age (HR 0.87 per 10-year increase, 95% CI 0.84-0.90), White race, in the Medicaid insurance programme (HR 1.22, 95% CI 1.07-1.40), tobacco smoking (HR 1.16, 95% CI 1.03-1.31) and having one or more emergency department visits in the year before a HS diagnosis. Absolute IRs of anxiety disorders were highest among patients with HS who were aged 18-29 years (7.10 per 100 PY), female (6.34 per 100 PY) and White (6.79 per 100 PY). CONCLUSIONS: HS is independently associated with an increased risk of anxiety disorders. An increased risk remains but is attenuated when confounders are controlled for. The relative risk may be particularly high in patients managed by dermatologists.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by painful skin lesions that often leak pus from sensitive areas of the body, including the arm pits, breasts, groin and perineum. The disease can flare in severity without notice. Due to the sensitive nature of the affected areas, unpredictability of the disease course and scarring that may occur because of chronic inflammation, HS is known to severely affect a person's quality of life. Some studies have linked HS to depression and anxiety. However, there is limited evidence describing which condition comes first, and the relationship is less well established among people from the USA with HS. This study aimed to investigate how many people with HS go on to develop a diagnosis of an anxiety disorder in the USA. We found that anxiety is more likely to develop in people with HS than in people without the disease. We also found that certain risk factors make a person with HS more likely to be diagnosed with anxiety, such as a history of depression, being female, being younger, being White, being an active cigarette smoker, being in the Medicaid insurance programme and making one or more visits to the emergency department in the year before their HS diagnosis. Overall, our study findings provide information on the association between HS and the development of anxiety, which is important to guide the clinical management of patients diagnosed with this skin condition.

Psychiatric disorders and mortality due to external causes following diagnosis of endometriosis at a young age: a longitudinal register-based cohort study in Finland.

BACKGROUND: Endometriosis diagnosed in adults is associated with increased risk of various psychiatric disorders. However, little is known concerning psychiatric comorbidity and mortality due to external causes associated with endometriosis diagnosed at a young age. OBJECTIVE: This longitudinal cohort study aimed to investigate the link between surgical diagnosis of endometriosis at a young age and subsequent psychiatric disorders and mortality due to external causes. In addition, we compared the occurrence of the most common psychiatric disorders between different sites of surgically confirmed endometriosis (ovarian vs other) because of possible differences in pain manifestations. STUDY DESIGN: We conducted a retrospective register-based cohort study. Altogether 4532 women with surgically confirmed diagnosis of endometriosis before the age of 25 years from 1987 to 2012 were identified from the Finnish Hospital Discharge Register. They were matched with women without surgically diagnosed endometriosis for age and municipality on the index day (n=9014). Women were followed up from the index day until the end of 2019 for the outcomes of interest, which included 9 groups of psychiatric disorders (inpatient episodes since 1987, outpatient episodes since 1998) and death due to external causes, including deaths due to accidents, suicides, and violence (Finnish Register of Causes of Death). Cox proportional hazard models were applied to assess the crude and parity-adjusted hazard ratios and 95% confidence intervals. RESULTS: The cohort's median age was 22.9 years (interquartile range, 21.3-24.1) at the beginning and 42.5 years (36.7-48.3) after a median follow-up time of 20.0 years (14.5-25.7). We observed a higher hazard of depressive, anxiety, and bipolar disorders in women with endometriosis compared with the reference cohort, with depressive and anxiety disorders being the two most common psychiatric disorders. These differences appeared early and remained the same during the entire follow-up, irrespective of whether assessed from the data on inpatient episodes only or the data on both in- and outpatient episodes. The corresponding adjusted hazard ratios were 2.57 (95% confidence interval, 2.11-3.14) and 1.87 (1.65-2.12) for depressive disorders, 2.40 (1.81-3.17) and 2.09 (1.84-2.37) for anxiety disorders, and 1.71 (1.30-2.26) and 1.66 (1.28-2.15) for bipolar disorders, respectively. A higher hazard was observed for nonorganic sleeping disorders for the first 10 years only (3.83; 2.01-7.30) when assessed using the data on both in- and outpatient episodes. When based on inpatient records, a higher hazard for alcohol/drug dependence after 15 years of follow-up (2.07; 1.21-3.54) was observed. The difference in hazard for personality disorders tended to increase during follow-up (<10 years, 2.12 [1.28-3.52]; ≥10 years, 3.08 [1.44-6.57]). Depressive and anxiety disorders occurred more frequently in women with types of endometriosis other than ovarian endometriosis. No difference in deaths due to external causes was observed between the endometriosis and reference cohorts. CONCLUSION: Surgical diagnosis of endometriosis at a young age was associated with increased incidence of several psychiatric disorders. Moreover, within the endometriosis population, psychiatric comorbidity was more common in women with types of endometriosis other than ovarian endometriosis. We speculate that chronic pain is essential in the development of these psychiatric disorders, and that early and effective pain management is important in reducing the risk of psychiatric morbidity in young women. More research concerning the associations and management of endometriosis and associated psychiatric disorders is warranted.

Annual Research Review: Health anxiety in children and adolescents-developmental aspects and cross-generational influences.

Health anxiety involves excessive worries about one's health along with beliefs one has an illness or may contract a serious disease. Concerning evidence suggests that health anxiety is on the rise in society, possibly further fueled by the COVID-19 pandemic. Recent classification systems acknowledge that impairing health-related worries and beliefs can emerge in early childhood with significant levels of symptoms persisting throughout childhood, and possibly continuous with diagnostic considerations in adulthood. This narrative review summarizes recent research advances in health anxiety in children and adolescents, focusing on various developmental aspects of health anxiety and related concepts in youths. Findings suggest that health anxiety symptoms in young age groups are associated with impairment, distress, and increased healthcare use, as well as substantial comorbidity with mainly other emotional problems and disorders. Furthermore, longitudinal studies suggest that childhood health anxiety can persist across adolescence, perhaps with links to chronic courses in adulthood. The growing literature was further reviewed, thus extending our understanding of early risk factors, including the potential role of exposure to serious illness and transgenerational transmission of health anxiety. Learning more about developmental trajectories will be highly relevant to inform strategies for early detection and prevention. While modified cognitive behavioral therapies in adults are successful in treating health anxiety, specific interventions have not yet been tested in youths. Given substantial overlaps with other psychopathology, it could be important to develop and explore more transdiagnostic and scalable approaches that take advantage of common factors in psychotherapy, while also including a wider perspective on potential familiar maladaptive illness cognitions and behaviors.

Commentary: Health anxiety in youth during 'COVID' - some thoughts prompted by Rask et al. (2024).

Researchers continue to count the short- and longer-term mental health costs for children and adolescents of the COVID-19 pandemic and the associated exceptional restrictions imposed by governments on their lives in an attempt to control the pandemic and its impacts. Despite being at low risk of serious physical illness from COVID-19 themselves, some studies have reported a decline in the mental health of many young people during the pandemic. Some have suggested that this could even create a risk for long-term morbidity. In this commentary, we reflect on the excellent article by Rask and colleagues on paediatric health anxiety and consider key research gaps for the field in general and for the specific challenges and questions posed by the COVID-19 pandemic and its legacy.

Stratifying early-onset emotional disorders: using genetics to assess persistence in young people of European and South Asian ancestry.

BACKGROUND: Depression and anxiety are the most common mental health problems in young people. Currently, clinicians are advised to wait before initiating treatment for young people with these disorders as many spontaneously remit. However, others develop recurrent disorder but this subgroup cannot be identified at the outset. We examined whether psychiatric polygenic scores (PGS) could help inform stratification efforts to predict those at higher risk of recurrence. METHODS: Probable emotional disorder was examined in two UK population cohorts using the emotional symptoms subscale of the Strengths and Difficulties Questionnaire (SDQ). Those with emotional disorder at two or more time points between ages 5 and 25 years were classed as 'recurrent emotional disorder' (n = 1,643) and those with emotional disorder at one time point as having 'single episode emotional disorder' (n = 1,435, controls n = 8,715). We first examined the relationship between psychiatric PGS and emotional disorders in childhood and adolescence. Second, we tested whether psychiatric PGS added to predictor variables of known association with emotional disorder (neurodevelopmental comorbidity, special educational needs, family history of depression and socioeconomic status) when discriminating between single-episode and recurrent emotional disorder. Analyses were conducted separately in individuals of European and South Asian ancestry. RESULTS: Probable emotional disorder was associated with higher PGS for major depressive disorder (MDD), anxiety, broad depression, ADHD and autism spectrum disorder (ASD) in those of European ancestry. Higher MDD and broad depression PGS were associated with emotional disorder in people of South Asian ancestry. Recurrent, compared to single-episode, emotional disorder was associated with ASD and parental psychiatric history. PGS were not associated with episode recurrence, and PGS did not improve discrimination of recurrence when combined with clinical predictors. CONCLUSIONS: Our findings do not support the use of PGS as a tool to assess the likelihood of recurrence in young people experiencing their first episode of emotional disorder.

Annual Research Review: Sex, gender, and internalizing conditions among adolescents in the 21st century - trends, causes, consequences.

Internalizing conditions of psychopathology include depressive and anxiety disorders; they most often onset in adolescence, are relatively common, and contribute to significant population morbidity and mortality. In this research review, we present the evidence that internalizing conditions, including depression and anxiety, as well as psychological distress, suicidal thoughts and self-harm, and fatal suicide, are considerably increasing in adolescent populations across many countries. Evidence indicates that increases are currently greatest in female adolescents. We present an epidemiological framework for evaluating the causes of these increases, and synthesize research on whether several established risk factors (e.g., age of pubertal transition and stressful life events) and novel risk factors (e.g., digital technology and social media) meet conditions necessary to be plausible causes of increases in adolescent internalizing conditions. We conclude that there are a multitude of potential causes of increases in adolescent internalizing conditions, outline evidence gaps including the lack of research on nonbinary and gender nonconforming populations, and recommend necessary prevention and intervention foci from a clinical and public health perspective.

Substance use outcomes from the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS).

BACKGROUND: Substance use problems and anxiety disorders are both highly prevalent and frequently cooccur in youth. The present study examined the benefits of successful anxiety treatment at 3-12 years after treatment completion on substance use outcomes (i.e. diagnoses and lifetime expected use). METHODS: The sample was from the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS), a naturalistic follow-up study to the Child/Adolescent Anxiety Multimodal Study (CAMS) which randomized youth to cognitive behavioral therapy (CBT; Coping cat), medication (sertraline), their combination, or pill placebo. The first CAMELS visit occurred an average of 6.5 years following CAMS randomization. Participants were 319 youth (65.4% of the CAMS sample), aged 7-17 years at CAMS baseline assessment with a mean age of 17.6 years (range: 11-26 years) at the time of the first CAMELS follow-up. Substance use outcomes included diagnoses as well as lifetime substance use (i.e. alcohol and tobacco use). RESULTS: Eleven of 319 (3.4%) CAMELS participants were diagnosed with a substance use disorder at the initial follow-up visit. When compared to the population lifetime rate of 11.4%, the rate of diagnoses in the posttreated sample was significantly lower. Additionally, rates of lifetime alcohol use were lower than population rates at the initial and final follow-up visits. Rates of lifetime tobacco use were similarly lower than lifetime population rates at the initial visit (driven by significantly lower rates in the CBT treatment condition), but higher by the final visit. Furthermore, treatment remission (but not treatment response) was associated with a lower rate of substance use diagnoses at the initial follow-up visit, although rates of lifetime alcohol and tobacco use did not differ by treatment outcome. CONCLUSIONS: Anxiety treatments confer a beneficial impact on problematic substance use (i.e. diagnoses) as well as on expected substance use (i.e. alcohol and tobacco use) for on average, a period of 6.5 years.

Evaluation of depressive and anxiety symptoms in childhood-onset systemic lupus erythematosus: Frequency, course, and associated risk factors.

BACKGROUND: Depressive and anxiety symptoms are common in childhood-onset systemic lupus erythematosus (cSLE), yet their etiology and course remain unclear. We investigated the frequency of depressive and anxiety symptoms longitudinally in youth with cSLE, and associated socio-demographic and disease factors. METHODS: Participants 8-18 years with cSLE completed baseline measures [demographic questionnaire, Center for Epidemiologic Studies Depression Scale for Children (CES-DC), Screen for Childhood Anxiety Related Disorders (SCARED), and psychiatric interview] and follow-up measures (CES-DC and SCARED) > 6 months later. Prevalence of clinically significant depressive (score >15 on CES-DC) or anxiety symptoms (score ≥25 on SCARED) was calculated at baseline and follow-up. Baseline psychiatric interview diagnoses were tabulated. Relationships between socio-demographics (neighborhood-level material deprivation, ethnic concentration, adverse childhood event history, psychiatric condition in a first-degree relative), disease-related factors (disease duration, major organ disease, disease activity, glucocorticoid use, comorbid medical condition) and baseline depressive and anxiety scores, were examined in linear regression models. Factors with univariate associations with p < 0.2 were included in multivariable adjusted models. RESULTS: At baseline, of 51 participants with a mean disease duration of 4.3 years (SD 2.7), 35% (n = 18) and 35% (n = 18) had clinically significant depressive and anxiety symptoms, respectively. Anxiety disorder was diagnosed by psychiatric interview in 14% (n = 7), depressive disorders in 6% (n = 3), and post-traumatic stress disorder in 4% (n = 2). Adverse childhood events and first-degree relative with psychiatric condition were present in 40% (n = 20) and 37% (n = 18), respectively. In multivariable regression analysis, baseline depressive symptoms were positively correlated with neighbourhood-level material deprivation (ß = 4.2, 95% CI [1.0, 7.3], p = 0.01) and psychiatric condition in a first-degree relative (ß = 7.3, 95% CI [2.2, 12.4], p = 0.006). No associations were found between baseline anxiety scores and patient factors. At a median follow-up of 13.5 months (IQR 10.5, 18) for CES-DC (n = 34) and SCARED (n = 44), depressive and anxiety symptoms were persistent (18%, n = 6; 16%, n = 7), and newly present (24%, n = 8; 16% n = 7) at follow-up. CONCLUSION: In this sample, depressive and anxiety symptoms were prevalent and persistent. Depressive symptoms correlated with neighborhood-level material deprivation, and family psychiatric history. These findings support routine psychosocial assessment in cSLE, and provision of appropriate resources.

Perceived Need for Mental Health Care in a Cohort of Persons With Inflammatory Bowel Disease.

BACKGROUND: Psychiatric comorbidity is common in inflammatory bowel disease (IBD) and can negatively affect disease outcomes. We explored the perceived need for mental health care among persons with IBD. STUDY: Persons with IBD completed self-report questionnaires, including the Hospital Anxiety and Depression Scale (HADS), and reported whether they wanted help with their mood. Each was also assessed using the Structured Clinical Interview for DSM-IV-TR Axis-I Disorders (SCIDs). We used logistic regression analyses to determine factors associated with the perceived need for mental health care. RESULTS: Of 245 participants, 28% met the criteria for a past diagnosis of depression or anxiety disorder by SCID, and nearly 23% met the criteria for a current diagnosis of depression or anxiety disorder. One-third (n = 74) reported a perceived need for mental health care. Among those meeting criteria for a current SCID diagnosis of depression or anxiety, only 58% reported needing mental health care. Need for mental health care was reported by 79% of persons currently treated for either depression or 71% treated for anxiety. Persons with a perceived need for mental health care had higher mean HADS for depression and HADS for anxiety scores and also higher IBD symptom activity scores. Of those reporting no perceived need for mental health care, 13% had a current diagnosis of depression or anxiety disorder by SCID; even fewer had symptoms of depression or anxiety. CONCLUSIONS: Symptoms of depression or anxiety are more important than a formal diagnosis of depression or anxiety in predicting which persons with IBD will perceive a need for mental health care.

The natural history of lifetime psychiatric disorders in patients with obsessive-compulsive disorder followed over half a century.

OBJECTIVE: Few long-term studies have examined the life-time prevalence of comorbid psychiatric conditions in patients with obsessive-compulsive disorder (OCD). We therefore studied the frequency of comorbid psychiatric disorders, and their relation to onset and prognosis, in patients with OCD who were followed for almost half a century. METHODS: During 1947-1953, 285 OCD patients were admitted as inpatients to a university hospital in Gothenburg, Sweden. Among those, 251 (88%) accepted a structured comprehensive psychiatric examination in 1954-1956. In 1989-1993, 176 survivors were eligible and 144 (response rate 82%) were re-examined. The same psychiatrist performed both examinations. OCD was diagnosed according to the Schneider criteria, and other mental disorders according to DSM-IV. Mean follow-up since onset was 47 years. RESULTS: The lifetime frequency of depressive disorders was 84.7% (major depression 43.8%), generalized anxiety disorder (GAD) 71.5%, panic anxiety disorder 47.9%, agoraphobia 52.1%, specific phobias 64.6%, social phobia 47.9%, paranoid conditions 40.3% (29.1% paranoid ideation), psychotic disorders 15.3%, alcohol abuse 13.2% (men 39%, women 3%) and substance abuse 17.4%. Specific phobia most often started before OCD, while depression had a varied onset in relation to OCD. Social phobia, agoraphobia, GAD, alcohol and substance abuse, psychotic disorders and paranoid conditions most often started after OCD. Presence of GAD, psychotic disorder and substance abuse worsened prognosis of OCD. CONCLUSION: Comorbid psychiatric conditions are common in OCD patients, and have onset throughout the course. OCD signals vulnerability for other psychiatric conditions, which are important to detect in clinical practice as they negatively affect the outcome.

Disease trajectory of high neuroticism and the relevance to psychiatric disorders: A retro-prospective cohort study.

BACKGROUND: Neuroticism is a psychological personality trait that has a significant impact on public health and is also a potential predisposing factor for adverse disease outcomes; however, comprehensive studies of the subsequently developed conditions are lacking. The starting point of disease trajectory in terms of genetic variation remains unclear. METHOD: Our study included 344,609 adult participants from the UK Biobank cohort who were virtually followed up from January 1, 1997. Neuroticism levels were assessed using 12 items from the Eysenck Personality Questionnaire. We performed a phenome-wide association analysis of neuroticism and subsequent diseases. Binomial tests and logistic regression models were used to test the temporal directionality and association between disease pairs to construct disease trajectories. We also investigated the association between polygenic risk scores (PRSs) for five psychiatric traits and high neuroticism. RESULTS: The risk for 59 diseases was significantly associated with high neuroticism. Depression, anxiety, irritable bowel syndrome, migraine, spondylosis, and sleep disorders were the most likely to develop, with hazard ratios of 6.13, 3.66, 2.28, 1.74, 1.74, and 1.71, respectively. The disease trajectory network revealed two major disease clusters: cardiometabolic and chronic inflammatory diseases. Medium/high genetic risk groups stratified by the PRSs of four psychiatric traits were associated with an elevated risk of high neuroticism. We further identified eight complete phenotypic trajectory clusters of medium or high genetic risk for psychotic, anxiety-, depression-, and stress-related disorders. CONCLUSION: Neuroticism plays an important role in the development of somatic and mental disorders. The full picture of disease trajectories from the genetic risk of psychiatric traits and neuroticism in early life to a series of diseases later provides evidence for future research to explore the etiological mechanisms and precision management.