“Enjoy your baby” Internet-based CBT for mothers with babies: a feasibility randomised control trial

Background: Postnatal depression is a global health problem with lasting effects on the family. Government policy is focussed on early intervention and increasing access to psychological therapies. There is a growing evidence base for the use of computerised CBT packages and this study investigated the feasibility of a CBT-based self-help internet intervention for new mothers. Objective: To assess the ability to recruit mothers, deliver an internet course, obtain follow-up data and evaluate what mothers think of the course. Design: A feasibility randomised control design was used to compare a waiting list control group (delayed access= DA) to the Enjoy Your Baby course (immediate access= IA). Measures were administered at baseline and 8 week follow-up. Methods: Adverts were placed in the Metro freesheet, on charity web pages, on social media, posters were put up in the community, and leaflets were handed out at mother and baby groups. Participants had to be 18 years old or over with a child less than 18 months old. The IA arm was given access to the course straight away. After 8 weeks all participants were asked to recomplete the original measures and those in the IA arm also gave feedback on the course. Participants in the DA arm were given access after recompleting the questionnaires. Due to a lack of follow-up data a small discussion group was conducted. Intervention: The course contains 4 core modules including helping mothers understand why they feel the way they do and helping them build closeness to their babies. Additional modules, worksheets and homework tasks were available. The DA group were given a list of additional support resources and services, and encouraged to seek additional help if required. All participants received weekly automated emails for 12 weeks as they worked through the course. It was not possible to deliver individualised support. 34 Results: Despite using a number of recruitment strategies, recruitment was lower and slower than anticipated, and attrition was high. 41 women, primarily recruited via the internet, were randomised (IA n=21, DA n=20). No significant differences were observed between participants in either arm at baseline and no statistically significant differences were identified when the demographics and baseline measures of participants who logged-on to the course were compared to those who did not, or when participants who completed follow-up measures were compared to those who did not. Pre and post intervention scores on the EPDS approached statistical significance (P=.059, r=.444) favouring the intervention arm. The discussion group suggested strengths of the course and recommended areas for improvement, including making the course more mobile friendly. Conclusion: Internet interventions show promise; however it is difficult to recruit mothers, engagement is low and attrition high. A number of recommendations are made and a further pilot or an internal pilot of a larger substantive study should be conducted to confirm recruitment and retention. Trial ID: ISRCTN90927910.

MRI indices of functional recovery following intracerebral implantation of a human neural stem cell line in a pre-clinical model of ischaemic stroke

Stem cell therapy for ischaemic stroke is an emerging field in light of an increasing number of patients surviving with permanent disability. Several allogenic and autologous cells types are now in clinical trials with preliminary evidence of safety. Some clinical studies have reported functional improvements in some patients. After initial safety evaluation in a Phase 1 study, the conditionally immortalised human neural stem cell line CTX0E03 is currently in a Phase 2 clinical trial (PISCES-II). Previous pre-clinical studies conducted by ReNeuron Ltd, showed evidence of functional recovery in the Bilateral Asymmetry test up to 6 weeks following transplantation into rodent brain, 4 weeks after middle cerebral artery occlusion. Resting-state fMRI is increasingly used to investigate brain function in health and disease, and may also act as a predictor of recovery due to known network changes in the post-stroke recovery period. Resting-state methods have also been applied to non-human primates and rodents which have been found to have analogous resting-state networks to humans. The sensorimotor resting-state network of rodents is impaired following experimental focal ischaemia of the middle cerebral artery territory. However, the effects of stem cell implantation on brain functional networks has not previously been investigated. Prior studies assessed sensorimotor function following sub-cortical implantation of CTX0E03 cells in the rodent post-stroke brain but with no MRI assessments of functional improvements. This thesis presents research on the effect of sub-cortical implantation of CTX0E03 cells on the resting- state sensorimotor network and sensorimotor deficits in the rat following experimental stroke, using protocols based on previous work with this cell line. The work in this thesis identified functional tests of appropriate sensitivity for long-term dysfunction suitable for this laboratory, and investigated non-invasive monitoring of physiological variables required to optimize BOLD signal stability within a high-field MRI scanner. Following experimental stroke, rats demonstrated expected sensorimotor dysfunction and changes in the resting-state sensorimotor network. CTX0E03 cells did not improve post-stroke functional outcome (compared to previous studies) and with no changes in resting-state sensorimotor network activity. However, in control animals, we observed changes in functional networks due to the stereotaxic procedure. This illustrates the sensitivity of resting-state fMRI to stereotaxic procedures. We hypothesise that the damage caused by cell or vehicle implantation may have prevented functional and network recovery which has not been previously identified due to the application of different functional tests. The findings in this thesis represent one of few pre-clinical studies in resting-state fMRI network changes post-stroke and the only to date applying this technique to evaluate functional outcomes following a clinically applicable human neural stem cell treatment for ischaemic stroke. It was found that injury caused by stereotaxic injection should be taken into account when assessing the effectiveness of treatment.