Rethinking the nature of mental disorder: a latent structure approach to data from three national psychiatric morbidity surveys

High levels of comorbidity between the anxiety and depressive disorders have raised questions about whether the diagnostic boundaries between these disorders need to be redrawn, or even whether both should be considered as different facets of a single disease process. Accordingly, latent class analysis has been used in several attempts to find data-driven groupings of individuals based on the symptoms of anxiety and depression. However, the assumption of conditional independence in this approach risks the extraction of spurious ‘severity classes’, making findings difficult to interpret. Factor mixture analysis relaxes that assumption by incorporating a common factor within each class, thereby overcoming the problem. This project investigated whether factor mixture analysis can suggest a data-driven classification of individuals based on the symptoms of common mental disorders. The analysis was based on pooled symptom-level data from three national psychiatric morbidity surveys of adults living in Great Britain carried out in 1993, 2000 and 2007. A comparison of the fit from the various latent variable models indicated that factor mixture models provided the best fit to the data, both in terms of model parsimony and goodness-of-fit. However, subsequent investigations suggested that the classes did not represent true groups in the population, but were rather accommodating violations of key assumptions in the standard factor model. Therefore, the results provide little guidance for revising the psychiatric classification. This is the first study to carry out an in-depth investigation into the interpretation of the extracted classes after applying factor mixture models to investigate the latent structure of mental disorders; its findings highlight the difficulties of interpreting the results of these models. Consequently, the thesis questions whether factor mixture models are actually useful for exploring the true nature of psychiatric disorders, and whether the present heavy use of such models is justified. An investigation of previously published examples suggests that their results may be prone to misinterpretation. The thesis concludes with a set of recommendations for the reporting of these models that may help to minimise the risks of such misinterpretation

Lithium Prescribing during Pregnancy: A UK Primary Care Database Study

Women taking lithium must decide whether to continue the medication if they conceive or plan to conceive. Little is known about the extent of prescribing of lithium during pregnancy

Body mass index and common mental disorders: exploring the shape of the association and its moderation by age, gender and education

Obesity is known to be associated with increased prevalence of common mental disorders (for example, depression and anxiety), and there is evidence of age and gender differences in this relationship. However, categorisation of body mass index (BMI) and age has limited our ability to understand the nature of these differences. This study used continuous values of BMI and age to explore the shape of the association between common mental disorders and BMI and whether it varied with age, gender and education

Antiepileptic drugs prescribed in pregnancy and prevalence of major congenital malformations: comparative prevalence studies.

OBJECTIVE: The aim of this study was to examine the prevalence of major congenital malformations associated with antiepileptic drug (AED) treatment in pregnancy. PATIENTS AND METHODS: Using data from The Health Improvement Network, we identified women who have given live birth and their offspring. Four subgroups were selected based on the AED treatment in early pregnancy, valproate, carbamazepine, lamotrigine and women not receiving AED treatment. We compared the prevalence of major congenital malformations within children of these four groups and estimated prevalence ratios (PRs) using Poisson regression adjusted for maternal age, sex of child, quintiles of Townsend deprivation score and indication for treatment. RESULTS: In total, 240,071 women were included in the study. A total of 229 women were prescribed valproate in pregnancy, 357 were prescribed lamotrigine and 334 were prescribed carbamazepine and 239,151 women were not prescribed AEDs. Fifteen out of 229 (6.6%) women prescribed valproate gave birth to a child with a major congenital malformation. The figures for lamotrigine, carbamazepine and women not prescribed AEDs were 2.7%, 3.3% and 2.2%, respectively. The prevalence of major congenital malformation was similar for women prescribed lamotrigine or carbamazepine compared to women with no AED treatment in pregnancy. For women prescribed valproate in polytherapy, the prevalence was fourfold higher. After adjustments, the effect of estimates attenuated, but the prevalence remained two- to threefold higher in women prescribed valproate. CONCLUSION: The results of our study suggest that lamotrigine and carbamazepine are safer treatment options than valproate in pregnancy and should be considered as alternative treatment options for women of childbearing potential and in pregnancy

Initiation and duration of selective serotonin reuptake inhibitor prescribing over time: UK cohort study

BACKGROUND: Recent media reports have focused on the large increase in antidepressants dispensed in England. We investigated this, focusing on selective serotonin reuptake inhibitors (SSRIs). AIMS: To examine the rate of initiation of SSRIs over time and changes over time in the duration of prescribing episodes. METHOD: We estimated initiation and duration of SSRI prescribing from 7 025 802 individuals aged over 18 years and registered with a general practice that contributed data to The Health Improvement Network. RESULTS: Rates of SSRI initiation increased from 1.03 per 100 person-years in 1995 to 2.15 in 2001, but remained stable from then to 2012. The median duration of prescribing episodes increased from 112 to 169 days for episodes starting in 1995 to 2010. CONCLUSIONS: Despite media reports describing an increasing rate of antidepressant prescribing, SSRI initiation rates have stabilised since 2001. However, our results suggest that individuals who take SSRIs are receiving treatment for longer

Discontinuation of antipsychotic medication in pregnancy: A cohort study.

Women prescribed antipsychotics face the dilemma on whether to continue medication in pregnancy in terms of balancing risks and benefits. Previous research on other psychotropic medications suggests that many women discontinue treatment in early pregnancy. However, very limited evidence exists on discontinuation of antipsychotic medication

The relation between neuromechanical parameters and Ashworth score in stroke patients

Quantifying increased joint resistance into its contributing factors i.e. stiffness and viscosity ("hypertonia") and stretch reflexes ("hyperreflexia") is important in stroke rehabilitation. Existing clinical tests, such as the Ashworth Score, do not permit discrimination between underlying tissue and reflexive (neural) properties. We propose an instrumented identification paradigm for early and tailor made interventions.BioMechanical EngineeringMechanical, Maritime and Materials Engineerin

Functional Organization of Locomotor Interneurons in the Ventral Lumbar Spinal Cord of the Newborn Rat

Although the mammalian locomotor CPG has been localized to the lumbar spinal cord, the functional-anatomical organization of flexor and extensor interneurons has not been characterized. Here, we tested the hypothesis that flexor and extensor interneuronal networks for walking are physically segregated in the lumbar spinal cord. For this purpose, we performed optical recordings and lesion experiments from a horizontally sectioned lumbar spinal cord isolated from neonate rats. This ventral hemi spinal cord preparation produces well-organized fictive locomotion when superfused with 5-HT/NMDA. The dorsal surface of the preparation was visualized using the Ca2+ indicator fluo-4 AM, while simultaneously monitoring motor output at ventral roots L2 and L5. Using calcium imaging, we provided a general mapping view of the interneurons that maintained a stable phase relationship with motor output. We showed that the dorsal surface of L1 segment contains a higher density of locomotor rhythmic cells than the other segments. Moreover, L1 segment lesioning induced the most important changes in the locomotor activity in comparison with lesions at the T13 or L2 segments. However, no lesions led to selective disruption of either flexor or extensor output. In addition, this study found no evidence of functional parcellation of locomotor interneurons into flexor and extensor pools at the dorsal-ventral midline of the lumbar spinal cord of the rat

The impact of laxative use upon symptoms in patients with proven slow transit constipation

<p>Abstract</p> <p>Background</p> <p>Constipation severity is often defined by symptoms including feelings of complete evacuation, straining, stool frequency and consistency. These descriptors are mostly obtained in the absence of laxative use. For many constipated patients laxative usage is ubiquitous and long standing. Our aim was to determine the impact of laxative use upon the stereotypic constipation descriptors.</p> <p>Methods</p> <p>Patients with confirmed slow transit constipation completed 3-week stool diaries, detailing stool frequency and form, straining, laxative use and pain and bloating scores. Each diary day was classified as being under laxative affect (laxative affected days) or not (laxative unaffected days). Unconditional logistic regression was used to assess the affects of laxatives on constipation symptoms.</p> <p>Results</p> <p>Ninety four patients with scintigraphically confirmed slow transit constipation were enrolled in the study. These patients reported a stool frequency of 5.6 ± 4.3 bowel motions/week, only 21 patients reported <3 bowel motions/week. Similarly, 21 patients reported a predominant hard stool at defecation. The majority (90%) of patients reported regular straining. A regular feeling of complete evacuation was reported in just 7 patients. Daily pain and/or bloating were reported by 92% of patients. When compared with laxative unaffected days, on the laxative affected days patients had a higher stool frequency (OR 2.23; <it>P </it><0.001) and were more likely to report loose stools (OR 1.64; <it>P </it><0.009). Laxatives did not increase the number of bowel actions associated with a feeling of complete evacuation. Laxative use had no affect upon straining, pain or bloating scores</p> <p>Conclusions</p> <p>The reporting of frequent and loose stools with abdominal pain and/or bloating is common in patients with slow transit constipation. While laxative use is a significant contributor to altering stool frequency and form, laxatives have no apparent affect on pain or bloating or upon a patients feeling of complete evacuation. These factors need to be taken into account when using constipation symptoms to define this population.</p