Mental health in the COVID-19 pandemic: A longitudinal analysis of the CLoCk cohort study.

BACKGROUND: Little is known about the long-term mental health consequences of the pandemic in children and young people (CYP), despite extremely high levels of exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus and the disruption to schooling and leisure activities due to the resultant restrictions. There are mixed findings from systematic reviews of how the pandemic affected CYP's mental health, which may be due to heterogeneous methods and poor quality studies. Most, but not all, suggest deterioration in mental health but population level studies may obscure the differing experiences of subgroups. The study questions are: (i) are there subgroups of CYP with distinct mental health profiles over the course of the second year of the Coronavirus Disease 2019 (COVID-19) pandemic (between April 2021 and May 2022); and (ii) do vulnerability factors influence CYP's mental health trajectories. METHODS AND FINDINGS: A matched longitudinal cohort study of non-hospitalised test-positive and test-negative 11- to 17-year-old CYP in England were recruited from the UK Health Security Agency having undergone PCR testing for COVID-19. They completed the Strengths and Difficulties Questionnaire (SDQ) at least twice over a 12-month follow-up period. Overall, 8,518 of 17,918 (47.5%) CYP who returned their first SDQ at 3 or 6 months post-testing were included in the analytical sample. Associations between age, sex, ethnicity, socioeconomic status (SES), and an educational health and care plan (EHCP, indicating special educational needs) on SDQ score trajectories were examined separately, after adjusting for PCR test result. Findings from multilevel mixed-effects linear regression model showed that on average mental health symptoms as measured by the total SDQ score increased over time (B = 0.11 (per month), 95% CI = 0.09 to 0.12, p < 0.001) although this increase was small and not clinically significant. However, associations with time varied by age, such that older participants reported greater deterioration in mental health over time (B = 0.12 (per month), 95% CI = 0.10 to 0.14 for 15 to 17y; 0.08 (95% CI = 0.06 to 0.10) for 11 to 14y; pinteraction = 0.002) and by sex, with greater deterioration in girls. Children with an EHCP experienced less deterioration in their mental health compared to those without an EHCP. There was no evidence of differences in rate of change in total SDQ by ethnicity, SES, or physical health. Those with worse prior mental health did not appear to be disproportionately negatively affected over time. There are several limitations of the methodology including relatively low response rates in CLoCk and potential for recall bias. CONCLUSIONS: Overall, there was a statistically but not clinically significant decline in mental health during the pandemic. Sex, age, and EHCP status were important vulnerability factors that were associated with the rate of mental health decline, whereas ethnicity, SES, and prior poor physical health were not. The research highlights individual factors that could identify groups of CYP vulnerable to worsening mental health.

Risk of new onset and persistent psychopathology in children with long-term physical health conditions: a population-based cohort study.

Children and young people (CYP) with long-term physical health conditions (pLTCs) have increased risk of psychopathology compared to physically healthier peers. We explored risk factors for new onset and persistent psychiatric disorders in CYP with pLTCs compared to CYP without pLTCs. This 3-year follow-up study involved a UK representative sample of CYP from the British Child and Adolescent Mental Health Surveys (N = 7804). We examined potential baseline predictors of new onset and persistent psychiatric disorders at follow-up in four groups of children based on the presence of any physical and/or any psychiatric conditions at baseline. Psychiatric disorders were assessed using standardised multi-informant diagnostic assessment. Separate multivariable binary logistic regressions were conducted for each group. In CYP with pLTCs, rented housing (aOR = 1.42, 95% CI 1.01 to 1.99), non-traditional family structure (aOR = 2.08, 95% CI 1.42 to 3.05), increased parental distress (aOR = 1.09, 95% CI 1.04 to 1.14), and greater peer relationship difficulties (aOR = 1.29, 95% CI 1.19 to 1.39) predicted future psychiatric disorder. Only peer relationship difficulties predicted persistent disorder (aOR = 1.27, 95% CI 1.17 to 1.38) in this group. A greater number of factors predicted the onset of psychiatric disorder in CYP with pLTCs compared to physically healthier peers and similarly, a higher number of factors predicted persistent disorder in CYP without pLTCs. CYP with pLTCs might comprise a group with different vulnerabilities, some of which are potentially tractable and may be useful indicators of patients who require preventable or management interventions.

Dysregulated responses to stress and weight in people with type 2 diabetes.

OBJECTIVE: Dysregulated stress responsivity has been linked with weight gain in healthy samples. However, the relationship between disturbances in stress-related biology and changes in weight in people with type 2 diabetes (T2D) is unclear. METHOD: A total of 66 participants with T2D underwent laboratory stress-testing in 2011-2012. Cardiovascular, neuroendocrine and inflammatory responses to standardised mental stress were assessed, and Body Mass Index (BMI) was measured. Participants self-reported information on BMI in 2019. Associations between stress-related biological responses and BMI at follow-up were modelled using linear regression adjusting for age, sex, resting biological levels and baseline BMI. RESULTS: Blunted diastolic blood pressure reactivity (B = -0.092, 95% CI -0.177; -0.007, p = 0.034) as well as poorer systolic blood pressure (B = -0.050, 95% CI -0.084; - 0.017, p = 0.004), diastolic blood pressure (B = -0.068, 95% CI -0.132; -0.004, p = 0.034) and heart rate (B = -0.122, 95% CI -0.015;-0.230, p = 0.027) recovery post-stress were associated with higher BMI 7.5 years later. Greater interleukin-1 receptor antagonist (B = 16.93, 95% CI 6.20; 27.67, p = 0.003) and monocyte chemoattractant protein-1 reactivity (B = 0.04, 95% CI 0.002; 0.084, p = 0.041) were associated with weight gain. No significant associations were detected for interleukin-6 or laboratory cortisol measures. CONCLUSION: Disturbances in stress-related biology may promote weight gain in people with T2D. Research with a larger sample size is required to explore associations between stress responsivity and BMI in people with T2D.

Natural course of health and well-being in non-hospitalised children and young people after testing for SARS-CoV-2: a prospective follow-up study over 12 months.

Background: Despite high numbers of children and young people (CYP) having acute COVID, there has been no prospective follow-up of CYP to establish the pattern of health and well-being over a year following infection. Methods: A non-hospitalised, national sample of 5086 (2909 SARS-COV-2 Positive; 2177 SARS-COV-2 Negative at baseline) CYP aged 11-17 completed questionnaires 6- and 12-months after PCR-tests between October 2020 and March 2021 confirming SARS-CoV-2 infection (excluding CYP with subsequent (re)infections). SARS-COV-2 Positive CYP was compared to age, sex and geographically-matched test-negative CYP. Findings: Ten of 21 symptoms had a prevalence less than 10% at baseline, 6- and 12-months post-test in both test-positives and test-negatives. Of the other 11 symptoms, in test-positives who had these at baseline, the prevalence of all symptoms declined greatly by 12-months. For CYP first describing one of these at 6-months, there was a decline in prevalence by 12-months. The overall prevalence of 9 of 11 symptoms declined by 12-months. As many CYP first described shortness of breath and tiredness at either 6- or 12-months, the overall prevalence of these two symptoms in test-positives appeared to increase by 6-months and increase further by 12-months. However, within-individual examination demonstrated that the prevalence of shortness of breath and tiredness actually declined in those first describing these two symptoms at either baseline or 6-months. This pattern was also evident for these two symptoms in test-negatives. Similar patterns were observed for validated measures of poor quality of life, emotional and behavioural difficulties, poor well-being and fatigue. Moreover, broadly similar patterns and results were noted for the sub-sample (N = 1808) that had data at baseline, 3-, 6- and 12-months post-test. Interpretation: In CYP, the prevalence of adverse symptoms reported at the time of a positive PCR-test declined over 12-months. Some test-positives and test-negatives reported adverse symptoms for the first time at six- and 12-months post-test, particularly tiredness, shortness of breath, poor quality of life, poor well-being and fatigue suggesting they are likely to be caused by multiple factors. Funding: NIHR/UKRI (ref: COVLT0022).

Trends in comorbid physical and mental health conditions in children from 1999 to 2017 in England.

INTRODUCTION: Children with long-term physical health conditions (pLTCs) are at increased risk of mental health conditions but less is known about time trends in the mental health of this group of children. METHODS: We used data from three comparable, population-based surveys of children conducted in 1999, 2004, and 2017. We examined whether the proportion of children aged 5-15 years old with comorbid mental health conditions (measured using the multi-informant Development and Well-being Assessment tool) and pLTCs (measured using parental report) in England increased from 1999 to 2017 using linear regression analysis. RESULTS: Our analysis used data from 8662 (1999), 6401 (2004) and 6219 (2017) children, respectively. The proportion of children with comorbid pLTCs and psychiatric disorders was 0.050 (95% CI = 0.045, 0.055) in 1999, 0.054 (95% CI = 0.049, 0.060) in 2004, and 0.059 (95% CI = 0.053, 0.065) in 2017. The linear regression model revealed a non-significant effect of time on the proportion of children with comorbid pLTCs and psychiatric disorders from 1999 to 2017 (B = 0.0004785; SE = 0.0001256; p = 0.163). CONCLUSION: The estimated prevalence of school-aged children with comorbid pLTCs and mental health conditions in England remained stable since 1999, highlighting the need to prioritize mental health resources for children with physical health comorbidities.

Predictors of contact with services for mental health problems among children with comorbid long-term physical health conditions: a follow-up study.

Children with long-term physical health conditions (pLTCs) are at increased risk of developing mental health comorbidities, although most do not access services for their mental health. No previous studies have examined the determinants of contact with services for mental health concerns among this group of children. This 3-year longitudinal study involved a population-based sample of children aged 5-16 years from the British Child and Adolescent Mental Health Surveys conducted in 1999 and 2004. In children with comorbid pLTCs and mental health disorders at baseline (N = 397), we examined associations between several child-, family- and service-related factors and (a) contact with primary health care, (b) contact with paediatrics and (c) contact with child and adolescent mental health services over 3-year follow-up (2002 and 2007). Separate multivariable binary logistic regressions were conducted for each service. The impact of mental health difficulties on the child and contact with the teacher predicted contact with all three services. Adolescent age, female gender, larger family size, some or marked academic difficulties, and having parents with educational qualification(s) were specific predictors of contact with primary health care. Male gender, stressful life events, and contact with primary health care were specific predictors of contact with child and adolescent mental health services. No other factors predicted contact with paediatrics. Our findings highlight the role of child-, family-, and service-related factors in accessing mental health care in children with comorbid pLTCs and mental health disorders which could inform planning and provision of services to reduce unmet mental health needs.

The importance of definitions in the measurement of long-term health conditions in childhood. Variations in prevalence of long-term health conditions in the UK using data from the Millennium Cohort Study, 2004-2015.

OBJECTIVES: To explore the impact of various measurements of long-term health conditions (LTCs) on the resulting prevalence estimates using data from a nationally representative dataset. METHODS: Children and young people in the Millennium Cohort Study were followed at ages 3, 5, 7, 11, and 14 years (N = 15,631). We estimated the weighted prevalence of LTCs at each time point and examined the degree to which estimates agreed with alternate health indicators (special educational needs and disability [SEND], specific chronic conditions, and common chronicity criteria) using descriptive analyses, Cohen's kappa statistic, and percentage agreement. RESULTS: The estimated weighted prevalence of LTCs peaked at 5 years old (20%). Despite high percentage agreement, we observed at best moderate chance-corrected agreement between the type of LTC and reasons for SEND (kappas from 0.02 to 0.56, percentage agreement from 97% to 99%) or specified chronic conditions (kappas from 0.002 to 0.02, percentage agreement from 73% to 97%). Applying chronicity criteria decreased the estimated weighted prevalence of LTCs (3%). CONCLUSION: How long-term conditions are defined drastically alters the estimated weighted prevalence of LTCs. Improved clarity and consistency in the definition and measurement of LTCs is urgently needed to underpin policy and commissioning of services.

Inflammatory stress responses and future mental health outcomes in people with type 2 diabetes.

Background: Inflammatory dysregulation may be linked with mental health disturbances in people with Type 2 Diabetes (T2D), however no previous studies have examined longitudinal associations between inflammatory stress responses and mental health outcomes in T2D. Purpose: To better understand the biological mechanisms that might predispose people with T2D to poor mental health in the future. Methods: At baseline, 140 participants with T2D participated in a laboratory stress testing study (mean age = 64 years). Participants underwent two mental stress tasks and blood was sampled before and up to 45 min post-stress to detect plasma interleukin (IL)-6. The Center for Epidemiological Studies-Depression scale and the Short Form-36 Health Survey were completed at baseline and 7.5 years later. We tested associations between IL-6 stress responses and a) depression symptoms and b) mental health-related quality of life (QoL) at baseline and at follow-up using linear regression analyses adjusting for age, sex, and body mass index (BMI). Results: Up to 66 participants provided follow-up data. In cross-sectional analyses, increased IL-6 stress responses immediately post-task were associated with lower mental health-related quality of life (B = -21.73, p = 0.005, 95% CI [-36.82, -6.63]) adjusting for age, sex, and BMI. In longitudinal analyses, increased IL-6 stress responses at 45 min post-task were associated with increased depressive symptoms (B = 10.31 p = 0.048, 95% CI [0.10, 20.51]) and decreased mental health-related QoL (B = -21.18 p = 0.031, 95% CI [-40.34, -2.02]) adjusting for age, sex, and BMI. The association between the 45-min IL-6 response and depressive symptoms at follow-up was diminished after further adjustment for physical health-related QoL and baseline depressive symptoms (B = 10.14, p = 0.055, 95% CI [-0.21,20.48]). Conclusions: This study supports the link between inflammatory stress responsivity and future mental health outcomes in people with T2D. Further research involving a larger sample size is required.

Mental health and school absenteeism in children with long-term physical conditions: A secondary analysis of the British Child and Adolescent Mental Health Surveys 2004 and 2007.

BACKGROUND: Children and young people (CYP) with long-term physical conditions (LTCs) are more likely to have poorer mental health and more school absenteeism compared with CYP with no LTCs. However, there is limited longitudinal research, and the extent to which these difficulties persist in CYP with LTCs is unknown. Furthermore, little is known about the relative impact of different types of LTC on mental health and absenteeism. METHODS: We investigated cross-sectional and longitudinal associations of different LTCs with mental health and school absenteeism in a large (N = 7977) nationally representative survey of CYP in Great Britain and its 3-year follow-up. Psychopathology was assessed using the parent-reported Strengths and Difficulties Questionnaire (SDQ), and diagnosis of any psychiatric disorder using the Development and Wellbeing Assessment (DAWBA). Days absent and persistent absence (missing 10% or more of school days) were reported by parents. RESULTS: Compared with those with no LTCs, CYP with any LTC had higher SDQ total difficulties scores at baseline (adjusted mean difference 1.4, 1.1-1.6) and follow-up (1.1, 0.8-1.4) and were more likely to have a psychiatric disorder at baseline (adjusted odds ratio [aOR] 1.59, 1.34-1.89) and follow-up (1.75, 1.44-2.12). Children with any LTC also missed more days of school at baseline (adjusted incidence rate ratio 1.47, 1.31-1.64) and follow-up (1.17, 1.00-1.36) and were more likely to be persistently absent (aOR baseline 1.78, 1.48-2.14; follow-up 1.27, 1.00-1.61). Neurodevelopmental disorders, migraines and atopic conditions were particularly strongly associated with both mental health and absenteeism. CONCLUSIONS: Children with LTCs had poorer mental health and more school absence than those with no LTCs. Clinicians should routinely enquire about mental health and school attendance in CYP with LTCs and should collaborate with families and schools to ensure these children are provided with sufficient mental health and educational support.

Enjoyment of life predicts reduced type 2 diabetes incidence over 12 years of follow-up: findings from the English Longitudinal Study of Ageing.

BACKGROUND: Subjective well-being appears to be associated with reduced risk of type 2 diabetes (T2D). However, it is unknown whether this association is similar across different types of well-being. We examined the relationship between hedonic and eudaimonic well-being and incident T2D, and explored the role of sociodemographic, behavioural and clinical factors in these associations. METHODS: We used data from 4134 diabetes-free participants from the English Longitudinal Study of Ageing (mean age =64.97). Enjoyment of life and purpose in life were assessed using items from the CASP-19 to reflect hedonic and eudaimonic well-being, respectively. Participants reported T2D diagnosis over 12 years. We used Cox proportional hazards regression analyses and also explored the percentage of association explained by different covariates. RESULTS: Results revealed a protective role for enjoyment of life in T2D rate adjusting for sociodemographic (age, sex, wealth, ethnicity, marital status), behavioural (physical activity, smoking, alcohol consumption, body mass index) and clinical (hypertension, coronary heart disease and glycated haemoglobin) characteristics (HR =0.93, p=0.021, 95% CI (0.87, 0.99)). Sociodemographic, behavioural and clinical factors accounted for 27%, 27% and 18% of the association, respectively. The relationship between purpose in life and T2D was non-significant (adjusted HR =0.92, p=0.288, 95% CI (0.78, 1.08)). CONCLUSION: This study illustrates how the link between subjective well-being and T2D varies between well-being components. It also demonstrates that sociodemographic, behavioural and clinical factors partially explain this association. Intervention studies examining whether changes in enjoyment of life can help delay T2D onset are warranted.

Diabetes-related distress and daily cortisol output in people with Type 2 diabetes.

AIMS: Diabetes-related distress is common in Type 2 Diabetes and is linked with poor diabetes control. However, mechanisms underlying this association are unclear. One pathway that could be involved is neuroendocrine dysfunction, as Type 2 Diabetes is associated with altered diurnal cortisol output. This study investigated the link between diabetes-related distress and diurnal cortisol output. METHODS: 134 people with Type 2 Diabetes provided 5 cortisol samples over the course of a day. Multivariate linear regression models were used to assess whether overall and sub-domains of diabetes-related distress measured by the Diabetes Distress Scale, predicted cortisol parameters (waking cortisol, cortisol awakening response, cortisol slope and evening cortisol). RESULTS: Physician-related distress was associated with greater waking (B = 2.747, p = .015) and evening cortisol (B = 1.375, p = .014), and a blunted cortisol awakening response (B = -3.472, p = .038) adjusting for age, sex, income, body mass index, smoking and time of awakening. No associations were detected for overall distress, emotional, interpersonal or regimen distress. CONCLUSION: Physician-related distress was associated with alterations in daily cortisol output. Longitudinal research is required to understand how physician-related distress is associated with diurnal cortisol patterning over time.

Subjective wellbeing as a determinant of glycated hemoglobin in older adults: longitudinal findings from the English Longitudinal Study of Ageing.

BACKGROUND: Previous research has shown an association between subjective wellbeing and incident diabetes. Less is known about the role of wellbeing for subclinical disease trajectories as captured via glycated hemoglobin (HbA1c). We aimed to explore the association between subjective wellbeing and future HbA1c levels, and the role of sociodemographic, behavioral and clinical factors in this association. METHODS: We used data from the English Longitudinal Study of Ageing for this study (N = 2161). Subjective wellbeing (CASP-19) was measured at wave 2 and HbA1c was measured 8 years later at wave 6. Participants were free from diabetes at baseline. We conducted a series of analyses to examine the extent to which the association was accounted for by a range of sociodemographic, behavioral and clinical factors in linear regression models. RESULTS: Models showed that subjective wellbeing (CASP-19 total score) was inversely associated with HbA1c 8 years later after controlling for depressive symptoms, age, sex, and baseline HbA1c (B = -0.035, 95% CI -0.060 to -0.011, p = 0.005). Inclusion of sociodemographic variables and behavioral factors in models accounted for a large proportion (17.0% and 24.5%, respectively) of the relationship between wellbeing and later HbA1c; clinical risk factors explained a smaller proportion of the relationship (3.4%). CONCLUSIONS: Poorer subjective wellbeing is associated with greater HbA1c over 8 years of follow-up and this relationship can in part be explained by sociodemographic, behavioral and clinical factors among older adults.

Loneliness and biological responses to acute stress in people with Type 2 diabetes.

Loneliness is linked with all-cause mortality and coronary heart disease. Altered neuroendocrine and inflammatory responses to stress constitute potential pathways linking loneliness and ill-health. Stress responsivity is modified in people with Type 2 diabetes, but it is unclear whether loneliness influences biological stress responses in this population. We assessed interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1RA), monocyte chemoattractant protein-1 (MCP-1), and cortisol responses to acute stress in 135 people with Type 2 diabetes. Loneliness was measured used the Revised UCLA Loneliness Scale. Loneliness was inversely associated with cortisol output poststress (B = -4.429, p = 0.019) independent of age, sex, education, marital status, body mass index, and smoking. Lonelier individuals had raised MCP-1 concentrations 75 min poststress independent of covariates (B = 0.713, p = 0.022). No associations between loneliness and IL-6 or IL-1RA concentrations were detected. These results suggest that loneliness is associated with disturbances in stress responsivity in people with diabetes, and the impact of loneliness on health in people with diabetes may be mediated in part through dysregulation of inflammatory and neuroendocrine systems. Future research is required to understand if such changes increase the risk of poorer outcomes in this population.

Sex differences in interleukin-6 stress responses in people with Type 2 diabetes.

People with Type 2 diabetes (T2D) show dysregulated inflammatory responses to acute stress, but the effect of sex on inflammatory responses in T2D remains unclear. The purpose of this study was to investigate differences in interleukin (IL)-6 stress responses between older men and women with T2D. One hundred and twenty-one people (76 men; mean age = 64.09, SD = 7.35, 45 women; mean age = 63.20, SD = 6.70) with doctor-verified T2D took part in this laboratory-based stress testing study. Participants carried out acute mental stress tasks, and blood was sampled at baseline, immediately poststress, 45 min poststress, and 75 min poststress to detect plasma IL-6 concentrations. IL-6 change scores were computed as the difference between the baseline measurement and the three time points poststress. Main effects and interactions were tested using mixed model analysis of covariance. We found a significant main effect of time on IL-6 levels, and a significant Sex × Time interaction. In adjusted analyses including the three change scores and all the covariates, the significant Sex × Time interaction was maintained; IL-6 responses were greater in women at 45 and 75 min poststress compared with men, adjusting for age, body mass index, smoking, household income, glycated hemoglobin, oral antidiabetic medication, insulin/other injectable antidiabetic medication, depressive symptoms, and time of day of testing. Different inflammatory stress response pathways are present in men and women with T2D, with women producing larger IL-6 increases. The long-term implications of these differences need to be elucidated in future studies.

Happiness and Inflammatory Responses to Acute Stress in People With Type 2 Diabetes.

BACKGROUND: Positive psychological characteristics in people with type 2 diabetes (T2D) are associated with better health and longevity, and one plausible physiological mechanism involves lower markers of inflammation. Positive affect is related to lower basal inflammatory markers and smaller inflammatory responses to acute stress, but this association in people with T2D remains to be examined. PURPOSE: To examine the relationship between happiness and inflammatory markers at baseline and in response to acute stress in people with T2D. METHODS: One hundred forty people with T2D took part in laboratory-based stress testing. We aggregated daily happiness ratings over 7 days before stress testing. During the laboratory session, participants underwent two mental stress tasks-the mirror tracing and the Stroop task. Blood was sampled at baseline and post-stress (up to 75 min post-stress) to detect plasma interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and monocyte chemoattractant protein-1 (MCP-1). Associations between happiness and inflammatory markers and responses were analyzed using multivariable linear regressions. RESULTS: Greater daily happiness significantly predicted lower baseline and post-stress IL-6 concentrations, and lower baseline MCP-1, after adjusting for covariates. The association between happiness and reduced basal IL-6 maintained after further controlling for daily sadness. We did not find significant associations between daily happiness and inflammatory responses to acute stress. No associations were detected for IL-1Ra. CONCLUSIONS: Happier individuals with T2D have lower inflammatory markers before and after acute stress, albeit independent of stress responsivity. Findings could provide a protective physiological pathway linking daily happiness with better health in people with T2D.