Pain which lasts for more than 3 months is termed chronic or persistent pain. It often occurs in the absence of obvious injury. It can be very difficult to treat. The UK is home to several large databases that contain information about subjects’ life history of pain and their genetic “make-up”. We plan to use the largest of these (UK Biobank) to help identify the genes that are related to the presence of a chronic pain condition (e.g. pain of duration >3 months) and the related symptoms experienced by sufferers e.g. low mood, poor sleep, lack of motivation, (pain) anxiety or pain depression. By gaining confidence that these genetic markers are related to the presence of a chronic pain condition, we will then use this information to recruit two small (each <200) groups of ALSPAC subjects who may or may not already have a pain condition. The beauty of this approach, is that by identifying the genes that make people susceptible to developing a pain condition, we will see how this interacts with health factors e.g. weight, blood pressure, and events that shape a person’s psychology e.g. adverse life events such as bereavement, to try to provide a means for people to modify their risk, or identify people for whom early intervention might be most beneficial following an injury – to hopefully avoid them going on to suffer life-long pain.

To achieve this goal, we would ask those subjects to undergo a series of pain tests (which of themselves cause only temporary discomfort) and undergo an MRI scan of their brain and spinal cord.

To better characterise pain present in the ALSPAC cohort, we propose to add pain-specific questionnaires (and tasks) to the upcoming age 30 clinics and questionnaires, which would target all participants. These questionnaires/tasks would explore the incidence of pain in the cohort, which will provide a more complete picture than is currently available. By adding information to this time point, we will gain insight to the cohort and to which genetic and biological factors can influence the development of a chronic pain condition. The availability of this window, where the majority of the cohort are still (hopefully) pain-free, will provide a baseline from which future studies will be able to reflect on the factors that ultimately led some participants to develop a chronic pain condition.

The remit of the Advanced Pain Discovery Platform funding call is to better understand the mechanisms associated with pain. Our Expression of Interest is focused on psychosocial mechanisms of pain, and as part of this we wish to see how these impact on individuals across the lifespan. We wish to explore potential psychosocial correlates of pain, and build on work already conducted by members of our consortium on pain. Details of this project will be updated in due course.

During adolescence there are changes in how adolescents experience and regulate their emotions, and this is related, in part by changes in the body related to puberty and development of the neuroendocrine system. These changes can begin at different ages for people, and can also be influenced by the general physical health of the person, as well as their life experience of stress, social relationships and learning opportunities. Physical health influences psychosocial development in several ways, and there is an accumulation of evidence that biomarkers of physical health, including markers of inflammation, cortisol levels, and other indicators of stress, influences when, and how, adolescents develop skills in emotional regulation and stress management. There is a related body of evidence that puberty, inflammation and stress interact to influence emotional experience in childhood and adolescence, and may influence mood, and the risk of mod disorders, for example anxiety and depression. Much of the research on the psychobiological predictors, correlates and consequences of mood and behaviour have been done with adults, and so there is still much to know about if and how adolescent development may be influenced by inflammation, biomarkers of stress and experiences, and further, how these interactions may be influenced by pubertal development.

Previous studies have reported that addictive behaviors decrease when infectious disease first occurs but increase as the disease continues. It shows that especially among health workers, the addiction problems can get even more serious compared to the period when the infectious disease did not occur. This study wants to examine predictive factors that are associated with addictive behaviors before and after Covid-19.

Depression is the leading cause of global disability with over 300 million people suffering world-wide. Estimates suggest that up to two thirds of patients do not recover following their first antidepressant treatment and up to one third do not recover after multiple treatments. Therefore, it is critically important to identify factors that predict recovery and reduce risk of relapse. Current methods in genetic epidemiology focus on predictors of mental illness onset. While this is crucial to prevent new diagnoses, it does little to help individuals already suffering. Therefore, the Recover project aims to extend current genetic epidemiology methods to better understand recovery from depression. The methods developed here will begin with a focus on depression but can also be extended to other mental illnesses. First, we will develop trajectories of depression using continuous longitudinal measures in two critical time points, 1) adolescence and early adulthood and 2) during and post pregnancy. Second, using these trajectories as outcomes we will explore many modifiable predictors of recovery. Third, we will use cutting-edge causal inference techniques to test whether or not these predictors are causal. And finally, we will develop novel technologies to capture fine-grained fluctuations in mood. Taken together, this work will lead to better interventions and inform adjuncts to treatment having real impact for the growing number of individuals suffering from depression.

Previous research has indicated that individuals with ADHD have an increased likelihood of developing mental health problems such as depression, anxiety and antisocial behavior. Despite mental health problems being increased in individuals with ADHD, not all children go on to develop poor mental health outcomes. Research has indicated that resilience is a dynamic process that arises from normal adaptive mechanisms and can be influenced by many factors. However, why some individuals with ADHD show higher levels of resilience and better outcomes compared to others is not yet well understood. One way of defining resilience is better-than-expected long-term mental health outcome than predicted by initial severity of childhood ADHD. Therefore, the current research project will focus on first identifying risk mechanisms which increase the likelihood of individuals with childhood ADHD developing adult mental health problems, and then will aim to identify potentially modifiable protective factors that could be the focus of prevention and intervention programs.

Epidemiological and clinical studies interested in circulating glucose as a risk factor or outcome typically measure levels in the blood at a single or widely spaced time points (e.g. every few years). While these are important health indicators, there has been an increasing appreciation that glucose levels and variability in free-living conditions during both the day and night, may also provide important health measures in clinical (e.g. diabetic or obese) and ‘healthy’ populations.

Continuous glucose monitoring (CGM) systems measure interstitial glucose levels ‘continuously’ by implanting a sensor subcutaneously. This produces a sequence of measurements for each participant (e.g. the average glucose level every 5 minutes over several days), that can be used to assess how a person’s glucose levels vary over both the day and night. We have recently published a novel software package called GLU, for deriving a consistent set of summary variables from CGM data. The derived summary variables can be used in analyses to assess how different characteristics of glucose levels and variability relate to health exposures and outcomes.

Individuals with Attention Deficit Hyperactivity Disorder (ADHD) have difficulties with sustaining attention, being overactive and being impulsive. It is one of the most common childhood disorders and causes difficulties in school, and with family relationships and friendships, whilst those with ADHD are also at higher risk of other difficulties such as anxiety and depression both in childhood and later life. Not all individuals with ADHD have the same problems though, so it is important to understand who is at greatest risk of them. Difficulties with attention or hyperactivity are present across many people whilst only some have sufficient problems to be diagnosed with ADHD. International guidelines indicate where the dividing line between having a diagnosis or not is set, but we know that individuals who do not meet this diagnostic threshold can still have difficulties due to their ADHD symptoms whilst even in those with a diagnosis, the specific constellation of problem behaviours differs between individuals. This project aims to examine how differences in the symptom presentation and impairments in children are linked to other difficulties they have in childhood and as they grow into adulthood. It will also look at how genetic risks for ADHD and other disorders are related to these different presentations. This will be examined in both the general population (the ALSPAC cohort) and a clinical sample of children with ADHD, with additional replication in other international cohorts.

Polycystic ovarian syndrome (PCOS) is a major health concern that affects up to 10% of reproductive-aged women. This complex, heterogeneous condition is often characterized by a triad of ovulatory dysfunction, hyperandrogenism, and cardiometabolic dysfunction. Despite extensive physiologic and genetic studies, the treatment of PCOS remains limited by an incomplete understanding of the pathophysiology of the disorder. Identification of the genetic variants and pathways associated with PCOS susceptibility may provide insights into the pathogenesis of the condition and potential targeted treatments.

We propose to study phenotypes in children that may be associated with PCOS, including obesity, dyslipidemia, and premature adrenarche. Premature adrenarche is a pediatric condition characterized by early production of adrenal androgens such as DHEAS and androstenedione and has been proposed to be a precursor to PCOS in girls. We will calculate a polygenic risk score for PCOS in prepubertal children and test for associations with premature adrenarche and associated cardiometabolic and hyperandrogenic outcomes and biochemical and anthropometric traits. In addition, we will examine these outcomes during the pre-pubertal period in girls who later develop a diagnosis of PCOS in adolescence and young adulthood.

The extension of PCOS genetics to prepubertal children provides the unique opportunity to 1) classify the PCOS pathways into ovarian-dependent factors and nonovarian-dependent factors and 2) characterize the pediatric phenotypes associated with PCOS genetic risk factors, and 3) understand the pre-pubertal manifestations of a future PCOS diagnosis. Overall, investigations in prepubertal children have the potential to provide valuable insights into the mechanisms of pathogenesis and targets for treatment for PCOS.