The size, burden and cost of disorders of the brain in the UK

Aim: The aim of this paper is to increase awareness of the prevalence and cost of psychiatric and neurological disorders (brain disorders) in the UK. Method: UK data for 18 brain disorders were extracted from a systematic review of European epidemiological data and prevalence rates and the costs of each disorder were summarized (2010 values). Results: There were approximately 45 million cases of brain disorders in the UK, with a cost of €134 billion per annum. The most prevalent were headache, anxiety disorders, sleep disorders, mood disorders and somatoform disorders. However, the five most costly disorders (€ million) were: dementia: €22,164; psychotic disorders: €16,717; mood disorders: €19,238; addiction: €11,719; anxiety disorders: €11,687. Apart from psychosis, these five disorders ranked amongst those with the lowest direct medical expenditure per subject (Peer reviewe

In Vitro and In Vivo Characterization of the Alkaloid Nuciferine

RationaleThe sacred lotus (Nelumbo nucifera) contains many phytochemicals and has a history of human use. To determine which compounds may be responsible for reported psychotropic effects, we used in silico predictions of the identified phytochemicals. Nuciferine, an alkaloid component of Nelumbo nucifera and Nymphaea caerulea, had a predicted molecular profile similar to antipsychotic compounds. Our study characterizes nuciferine using in vitro and in vivo pharmacological assays.MethodsNuciferine was first characterized in silico using the similarity ensemble approach, and was followed by further characterization and validation using the Psychoactive Drug Screening Program of the National Institute of Mental Health. Nuciferine was then tested in vivo in the head-twitch response, pre-pulse inhibition, hyperlocomotor activity, and drug discrimination paradigms.ResultsNuciferine shares a receptor profile similar to aripiprazole-like antipsychotic drugs. Nuciferine was an antagonist at 5-HT2A, 5-HT2C, and 5-HT2B, an inverse agonist at 5-HT7, a partial agonist at D2, D5 and 5-HT6, an agonist at 5-HT1A and D4 receptors, and inhibited the dopamine transporter. In rodent models relevant to antipsychotic drug action, nuciferine blocked head-twitch responses and discriminative stimulus effects of a 5-HT2A agonist, substituted for clozapine discriminative stimulus, enhanced amphetamine induced locomotor activity, inhibited phencyclidine (PCP)-induced locomotor activity, and rescued PCP-induced disruption of prepulse inhibition without induction of catalepsy.ConclusionsThe molecular profile of nuciferine was similar but not identical to that shared with several approved antipsychotic drugs suggesting that nuciferine has atypical antipsychotic-like actions

Part-time work and health among older workers in Ireland and Britain

Part-Time (PT) work is viewed as a viable option for people who wish to have a gradual transition to retirement. From a policy viewpoint, this may help to alleviate some labour supply shortages and fiscal pressures, especially in the context of the ageing population. Factors such as health or pension provision may influence a person's decision to work PT. This article considers the impact of health on the work decision of people aged 50 and over in the UK and Ireland. Methodological issues are discussed and the impact of unobserved individual effects is estimated using the Mundlak (1978) estimator applied to the multinomial probit model. We find that health problems increase the probability of retirement for this age group in both countries. In Britain, those with health problems are less likely to work full time and more likely to work PT, however in Ireland, health problems appear to have no effect on the probability of PT work. This article discusses the potential reasons for these impacts and current policies on PT work.

Increased 4-hydroxynonenal protein adducts in male GSTA4-4/PPAR-α double knockout mice enhance injury during early stages of alcoholic liver disease

To test the significance of lipid peroxidation in the development of alcoholic liver injury, an ethanol (EtOH) liquid diet was fed to male 129/SvJ mice (wild-type, WT) and glutathione S-transferase A4-4-null (GSTA4-/-) mice for 40 days. GSTA4-/- mice were crossed with peroxisome proliferator-activated receptor-\u3b1-null mice (PPAR-\u3b1-/-), and the effects of EtOH in the resulting double knockout (dKO) mice were compared with the other strains. EtOH increased lipid peroxidation in all except WT mice (P < 0.05). Increased steatosis and mRNA expression of the inflammatory markers CXCL2, tumor necrosis factor-\u3b1 (TNF-\u3b1), and \u3b1-smooth muscle actin (\u3b1-SMA) were observed in EtOH GSTA4-/- compared with EtOH WT mice (P < 0.05). EtOH PPAR-\u3b1-/- mice had increased steatosis, serum alanine aminotransferase (ALT), and hepatic CD3+ T cell populations and elevated mRNA encoding CD14, CXCL2, TNF-\u3b1, IL-6, CD138, transforming growth factor-\u3b2, platelet-derived growth factor receptor-\u3b2 (PDGFR-\u3b2), matrix metalloproteinase (MMP)-9, MMP-13, \u3b1-SMA, and collagen type 1 compared with EtOH WT mice. EtOH-fed dKO mice displayed elevation of periportal hepatic 4-hydroxynonenal adducts and serum antibodies against malondialdehyde adducts compared with EtOH feeding of GSTA4-/-, PPAR-\u3b1-/-, and WT mice (P < 0.05). ALT was higher in EtOH dKO mice compared with all other groups (P < 0.001). EtOH-fed dKO mice displayed elevated mRNAs for TNF-\u3b1 and CD14, histological evidence of fibrosis, and increased PDGFR, MMP-9, and MMP-13 mRNAs compared with the EtOH GSTA4-/- or EtOH PPAR-\u3b1-/- genotype (P < 0.05). These findings demonstrate the central role lipid peroxidation plays in mediating progression of alcohol-induced necroinflammatory liver injury, stellate cell activation, matrix remodeling, and fibrosis

Associations between COVID-19 lockdown and post-lockdown on the mental health of pregnant women, postpartum women and their partners from the Queensland family cohort prospective study

Background: There are very few developed countries where physical isolation and low community transmission has been reported for COVID-19 but this has been the experience of Australia. The impact of physical isolation combined with low disease transmission on the mental health of pregnant women is currently unknown and there have been no studies examining the psychological experience for partners of pregnant women during lockdown. The aim of the current study was to examine the impact of the first COVID-19 lockdown in March 2020 and post lockdown from August 2020 on the mental health of pregnant women or postpartum women and their partners. Methods: Pregnant women and their partners were prospectively recruited to the study before 24 weeks gestation and completed various questionnaires related to mental health and general wellbeing at 24 weeks gestation and then again at 6 weeks postpartum. The Depression, Anxiety and Stress Scale (DASS-21) and the Edinburgh Postnatal Depression Scale (EPDS) were used as outcome measures for the assessment of mental health in women and DASS-21 was administered to their partners. This analysis encompasses 3 time points where families were recruited; before the pandemic (Aug 2018-Feb 2020), during lockdown (Mar-Aug 2020) and after the first lockdown was over (Sept-Dec 2020). Results: There was no significant effect of COVID-19 lockdown and post lockdown on depression or postnatal depression in women when compared to a pre-COVID-19 subgroup. The odds of pregnant women or postpartum women experiencing severe anxiety was more than halved in women during lockdown relative to women in the pre-COVID-19 period (OR = 0.47; 95%CI: 0.27–0.81; P = 0.006). Following lockdown severe anxiety was comparable to the pre-COVID-19 women. Lockdown did not have any substantial effects on stress scores for pregnant and postpartum women. However, a substantial decrease of over 70% in the odds of severe stress was observed post-lockdown relative to pre-COVID-19 levels. Partner’s depression, anxiety and stress did not change significantly with lockdown or post lockdown. Conclusion: A reproductive age population appear to be able to manage the impact of lockdown and the pandemic with some benefits related to reduced anxiety.</p

The social predictors of paternal antenatal mental health and their associations with maternal mental health in the Queensland Family Cohort prospective study

Antenatal depression (AND) affects 1 in 10 fathers, potentially negatively impacting maternal mental health and well-being during and after the transition to parenthood. However, few studies have assessed the social predictors of paternal AND or their possible associations with maternal mental health. We analysed data from 180 couples participating in the Queensland Family Cohort longitudinal study. Both parents completed surveys measuring mental health, relationship quality, social support, and sleep quality at 24 weeks of pregnancy. Mothers also completed the same surveys 6 weeks’ postpartum. Antenatal depression, stress, and anxiety were highest among fathers reporting lower social support and higher sleep impairment. Maternal AND, stress, and anxiety were higher among mothers reporting higher physical pain and poor sleep quality. Postnatally, mothers reporting lower social support also reported higher depression, anxiety, stress, and psycho-social well-being. While there were no significant associations between AND among fathers and maternal antenatal or postnatal depression, an exploratory analysis revealed that mothers whose partners reported lower antenatal social support also reported lower postnatal social support and higher postnatal depression. Our findings highlight the importance of including data among fathers to achieve a whole family approach to well-being during the transition to parenthood.</p