Sex-specific disruption of murine midbrain astrocytic and dopaminergic developmental trajectories following antenatal GC treatment

The mammalian midbrain dopaminergic systems arising in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) are critical for coping behaviours and are implicated in neuropsychiatric disorders where early life challenges comprise significant risk factors. Here, we aimed to advance our hypothesis that glucocorticoids (GCs), recognised key players in neurobiological programming, target development within these systems, with a novel focus on the astrocytic population. Mice received antenatal GC treatment (AGT) by including the synthetic GC, dexamethasone, in the mothers' drinking water on gestational days 16-19; controls received normal drinking water. Analyses of regional shapes and volumes of the adult SNc and VTA demonstrated that AGT induced long-term, dose-dependent, structural changes that were accompanied by profound effects on astrocytes (doubling/tripling of numbers and/or density). Additionally, AGT induced long-term changes in the population size and distribution of SNc/VTA dopaminergic neurons, confirming and extending our previous observations made in rats. Furthermore, glial/neuronal structural remodelling was sexually dimorphic and depended on the AGT dose and sub-region of the SNc/VTA. Investigations within the neonatal brain revealed that these long-term organisational effects of AGT depend, at least in part, on targeting perinatal processes that determine astrocyte density and programmed cell death in dopaminergic neurons. Collectively, our characterisation of enduring, AGT-induced, sex-specific cytoarchitectural disturbances suggests novel mechanistic links for the strong association between early environmental challenge (inappropriate exposure to excess GCs) and vulnerability to developing aberrant behaviours in later life, with translational implications for dopamine-associated disorders (such as schizophrenia, ADHD, autism, depression), which typically show a sex bias

Do financial distress and liquidity crises affect value and size premiums?

This study investigates the impact of liquidity crises on the relationship between stock (value and size) premiums and default risk in the US market. It first examines whether financial distress can explain value and size premiums, and then, subsequently, aims to determine whether liquidity crises increase the risk of value and size premium investment strategies. The study employs a time-varying approach and a sample of US stock returns for the period between January 1982 and March 2011, a period which includes the current liquidity crisis, so as to examine the relationship between default risk, liquidity crises and value and size premiums. The findings indicate that the default premium has explanatory power for value and size and premiums, which affect firms with different characteristics. We also find that liquidity crises may actually increase the risks related to size and value premium strategies.

How women use and experience western herbal practice for distress: implications for health care and self-management approaches.

Introduction: In the UK, common mental health disorders account for one in five of all work days lost, and cost employers £25bn each year. Herbal medicine has been shown to potentially be of use for mental distress, including conditions like anxiety. In 2008, 35% of British adults surveyed claimed to have used herbal medicine at some stage, the majority of whom were women. However, there is little research into how the users of western herbal medicine (WHM) experience the practice of herbal medicine, or how these experiences may change over time. Our research is studying women in the south-east of the UK who are suffering from distress (either as a primary complaint, or associated with another condition) who are seeking the services of a herbalist who practices WHM. Aim: To investigate the experiences of western herbal practice by women who are suffering with distress. Methods: The study is using semi-structured interviews of around thirty women, to elicit patient narratives at two time points. Thematic analysis is being used to consider how distressed women perceive and experience their distress, their reasons for using WHM, what contribution the women perceive the consultation and treatment with WHM may or may not make to their wellbeing, and whether their experiences change over time. Currently, sixteen women have been interviewed, and a preliminary thematic analysis has commenced. Results: Preliminary finding suggest that not only do women internalise their distress, but that they are surprisingly isolated in how they deal with it, whilst some also express social embarrassment about their experiences. The women perceived that their distress is not always considered seriously from their medical practitioners’ point of view. These women are drawn to herbalists not only in a search for effective treatment, but also to be given time to have their story heard, to form a collaborative relationship, and to attempt to regain some control of their life. The herbal treatment is valued due to its perceived naturalness, and reduced risk of adverse side effects. Nevertheless, WHM is just one of a number of self-care strategies that women utilise to help manage their distress. Discussion: Effective treatment is not only dependent upon the herbs, but also upon an effective therapeutic relationship. Feeling that the herbalist hears their story, provides a treatment plan that is individually tailored to the patient, and is available (even outside of the consultation) are all important in helping to establish this relationship.

Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory

RATIONALE: Antenatal exposure to the glucocorticoid dexamethasone dramatically increases the number of mesencephalic dopaminergic neurons in rat offspring. However, the consequences of this expansion in midbrain dopamine (DA) neurons for behavioural processes in adulthood are poorly understood, including working memory that depends on DA transmission in the prefrontal cortex (PFC). OBJECTIVES: We therefore investigated the influence of antenatal glucocorticoid treatment (AGT) on the modulation of spatial working memory by a D1 receptor agonist and on D1 receptor binding and DA content in the PFC and striatum. METHODS: Pregnant rats received AGT on gestational days 16-19 by adding dexamethasone to their drinking water. Male offspring reared to adulthood were trained on a delayed alternation spatial working memory task and administered the partial D1 agonist SKF38393 (0.3-3 mg/kg) by systemic injection. In separate groups of control and AGT animals, D1 receptor binding and DA content were measured post-mortem in the PFC and striatum. RESULTS: SKF38393 impaired spatial working memory performance in control rats but had no effect in AGT rats. D1 binding was significantly reduced in the anterior cingulate cortex, prelimbic cortex, dorsal striatum and ventral pallidum of AGT rats compared with control animals. However, AGT had no significant effect on brain monoamine levels. CONCLUSIONS: These findings demonstrate that D1 receptors in corticostriatal circuitry down-regulate in response to AGT. This compensatory effect in D1 receptors may result from increased DA-ergic tone in AGT rats and underlie the resilience of these animals to the disruptive effects of D1 receptor activation on spatial working memory.

“Considering there’s supposedly nothing wrong with me, it’s not a life”: Women’s Narratives of Distress, Visiting Herbalists, and Being Well in the 21st Century

Distress can have a profoundly negative impact on the well-being of women (who are the main receivers of treatment for distress). Distress also poses a huge financial problem for the United Kingdom, the cost of which is predicted to reach over £26bn by 2026. A growing body of research has shown that various medicinal plants have potential to treat different aspects of distress. However, there is little research investigating the patient experience of western herbal practice (WHP), and none investigating women’s experiences of WHP for distress. In response, this longitudinal study utilised interviews with twenty-six women who were visiting herbalists for distress across the south-east of The United Kingdom to elicit their stories of distress, as well as their experiences of WHP. The narratives were analysed from a constructionist standpoint, using inductive thematic analysis. The participants’ narratives highlighted the profound impact of everyday distress, whilst feelings associated with distress (anxiety, low mood, isolation, shame and guilt) were frequently communicated via the use of metaphors. These negative feelings, often combined with unsuccessful biomedical encounters, frequently led to the women feeling desperate when first visiting a herbalist. The participants’ experiences of WHP showed that an accessible practitioner and good therapeutic relationship combined with flexible herbal treatment, allowed women with diverse stories of distress to overcome feelings of desperation. Ongoing support allowed the women to feel like they had a safety net as they journeyed from a place of distress, back into the wider world. These findings were supported by more unusual negative accounts, which showed how the herbal therapeutic process could be unsuccessful if elements were missing. This research is of significance as it helps to deepen our understanding of women’s experiences of distress – particularly perceptions of stigma which surround feelings of shame (linked to an inability to cope) and guilt (linked to the perceived impact of distress on others). The research also has relevance for WHP, as it highlights which positive aspects of WHP are of particular importance to women patients who are living with distress.