Proteomic and clinical insights into polycystic ovary syndrome in adolescents

Despite its high prevalence, our understanding of the pathophysiology of polycystic ovary syndrome (PCOS) is lacking. Consequently, the way we diagnose and manage this common condition is inadequate, which is especially true for adolescents. This thesis aims to expand the body of knowledge regarding PCOS in adolescents. It will explore the clinical phenotype of PCOS, in addition to using proteomic techniques to better understand the biological mechanisms which underpin this condition. However, to do this, we must first comprehend ‘normal’ menstrual patterns in these pubertal years. As such, this thesis begins by seeking to define menstrual and ovulatory ‘normality’ in the first year following menarche, by systematically reviewing relevant literature. Following this, data are presented from a longitudinal study evaluating the clinical presentation and phenotype of adolescents with a suspected diagnosis of PCOS. The latter part of the thesis focuses on the use of proteomic techniques to broaden our understanding of PCOS. Discovery proteomic analysis of urine samples is employed firstly to explore the biological pathways associated with PCOS, and secondly to identify specific proteins which are differentially expressed in adolescents with PCOS, which may form a pool of non-invasive candidate biomarkers. Inflammation was identified as the most significant biological process associated with PCOS in discovery analysis, and these findings were validated in subsequent targeted proteomic panels. Validation studies were undertaken in a larger cohort of adolescents with PCOS, and then comparison was also made to adults with PCOS. Finally, all results from this thesis are summarised, the findings discussed, and their implications considered, alongside future work

Characteristics of 698 patients with dissociative seizures: a UK multicenter study

Objective We aimed to characterize the demographics of adults with dissociative (nonepileptic) seizures, placing emphasis on distribution of age at onset, male:female ratio, levels of deprivation, and dissociative seizure semiology. Methods We collected demographic and clinical data from 698 adults with dissociative seizures recruited to the screening phase of the CODES (Cognitive Behavioural Therapy vs Standardised Medical Care for Adults With Dissociative Non‐Epileptic Seizures) trial from 27 neurology/specialist epilepsy clinics in the UK. We described the cohort in terms of age, age at onset of dissociative seizures, duration of seizure disorder, level of socioeconomic deprivation, and other social and clinical demographic characteristics and their associations. Results In what is, to date, the largest study of adults with dissociative seizures, the overall modal age at dissociative seizure onset was 19 years; median age at onset was 28 years. Although 74% of the sample was female, importantly the male:female ratio varied with age at onset, with 77% of female but only 59% of male participants developing dissociative seizures by the age of 40 years. The frequency of self‐reported previous epilepsy was 27%; nearly half of these epilepsy diagnoses were retrospectively considered erroneous by clinicians. Patients with predominantly hyperkinetic dissociative seizures had a shorter disorder duration prior to diagnosis in this study than patients with hypokinetic seizures (P < .001); dissociative seizure type was not associated with gender. Predominantly hyperkinetic seizures were most commonly seen in patients with symptom onset in their late teens. Thirty percent of the sample reported taking antiepileptic drugs; this was more common in men. More than 50% of the sample lived in areas characterized by the highest levels of deprivation, and more than two‐thirds were unemployed. Significance Females with dissociative seizures were more common at all ages, whereas the proportion of males increased with age at onset. This disorder was associated with socioeconomic deprivation. Those with hypokinetic dissociative seizures may be at risk for delayed diagnosis and treatment