Steroid-induced mania in a patient with previously well-controlled organic bipolar 1-like affective disorder secondary to acquired brain injury: case report and literature review.

Steroid-induced neuropsychiatric sequelae are common, and pose significant risks to people usually receiving glucocorticoids in the context of physical illness. Steroid-induced mania and hypomania are the most common of the acute complications, yet despite great progress in understandings in neurophysiology there are no recent studies which review the factors which might predict who will experience this severe complication, nor are there consensus guidelines on management. We report the unusual case of a woman in her 50s admitted to a psychiatric unit with steroid-induced mania despite compliance with two mood stabilisers, several days after the administration of a Dexamethasone and Docetaxel chemotherapy regime adjunctive to lumpectomy for breast cancer. She had previously been diagnosed with an organic affective disorder (with classical bipolar 1 pattern) following severe ventriculitis related to ventricular drain insertion for obstructive hydrocephalus secondary to a colloid cyst. She had no psychiatric illness before this brain injury, but has a maternal history of idiopathic bipolar 1 affective disorder. Her episode of steroid-induced mania resolved following use of sedative medications, continuation of her existing mood stabilisers, and reductions of the steroid dosing in collaboration with her oncology team, which also protected her from further manic relapses during continued chemotherapy. Established mental illness, a family history, and acquired brain injury may reflect risk factors for steroid-induced mania through currently unclear pathways. Future epidemiological studies could better confirm these observations, and basic neuroscience may look to further explore the role of extrinsic glucocorticoids in the pathophysiology of affective disorders.

Severe COVID anxiety among adults in the United Kingdom: cohort study and nested feasibility trial.

BACKGROUND: People with severe COVID anxiety have poor mental health and impaired functioning, but the course of severe COVID anxiety is unknown and the quality of evidence on the acceptability and impact of psychological interventions is low. METHODS: A quantitative cohort study with a nested feasibility trial. Potential participants aged 18 and over, living in the UK with severe COVID anxiety, were recruited online and from primary care services. We examined levels of COVID anxiety in the six months after recruitment, and factors that influenced this, using linear regression. Those scoring above 20 on the short Health Anxiety Inventory were invited to participate in a feasibility trial of remotely delivered Cognitive Behavioural Therapy for Health Anxiety (CBT-HA). Exclusion criteria were recent COVID-19, current self-isolation, or current receipt of psychological treatment. Key outcomes for the feasibility trial were the level of uptake of CBT-HA and the rate of follow-up. RESULTS: 204 (70.2%) of 285 people who took part in the cohort study completed the six month follow-up, for whom levels of COVID anxiety fell from 12.4 at baseline to 6.8 at six months (difference = -5.5, 95% CI = -6.0 to -4.9). Reductions in COVID anxiety were lower among older people, those living with a vulnerable person, those with lower baseline COVID anxiety, and those with higher levels of generalised anxiety and health anxiety at baseline. 36 (90%) of 40 participants enrolled in the nested feasibility trial were followed up at six months. 17 (80.9%) of 21 people in the active arm of the trial received four or more sessions of CBT-HA. We found improved mental health and social functioning among those in the active, but not the control arm of the trial (Mean difference in total score on the Work and Social Adjustment Scale between baseline and follow up, was 9.7 (95% CI = 5.8-13.6) among those in the active, and 1.0 (95% C.I. = -4.6 to 6.6) among those in the control arm of the trial. CONCLUSIONS: While the mental health of people with severe COVID anxiety appears to improve over time, many continue to experience high levels of anxiety and poor social functioning. Health anxiety is highly prevalent among people with severe COVID anxiety and may provide a target for psychological treatment. TRIAL REGISTRATION: Retrospectively registered at ISRCTN14973494 on 09/09/2021.

Perinatal mental health in medical school curricula: a national scoping survey of British universities and student psychiatry societies.

AIMS AND METHOD: With increasing recognition of the prevalence and impact of perinatal mental health (PMH) disorders comes a responsibility to ensure that tomorrow's doctors can support families during the perinatal period. Online surveys seeking information about the inclusion of PMH education in undergraduate curricula were sent to psychiatry curriculum leads and student psychiatry societies from each university medical school in the UK between April and September 2021. RESULTS: Responses were received from 32/35 (91.4%) medical schools. Two-thirds reported specific inclusion of PMH content in the core curriculum, typically integrated into general adult psychiatry or obstetric teaching. Students at the remaining schools were all likely to be examined on the topic or see perinatal cases during at least one clinical attachment. CLINICAL IMPLICATIONS: PMH education offers an opportunity for collaboration between psychiatry and other disciplines. Future work looking at educational case examples with objective outcomes would be valuable.

Interventions to improve the sleep quality of adults with personality disorder: A systematic review.

Poor quality sleep is common for people who have a diagnosis of personality disorder (PD). Core cognitive and behavioral features of PD may cause and perpetuate poor sleep, but to date, no review has collated the evidence on the efficacy of interventions to improve sleep quality for people with PD. Structured searches for interventional studies among adults with PD and reporting validated measures of sleep quality were conducted up to November 2022 in multiple databases. Single-case reports were excluded. Study quality was assessed with standardized risk of bias tools. Unreported data was sought systematically from authors. This review was pre-registered with an international prospective register of systematic reviews (PROSPERO) (CRD42021282105). Of the 3503 identified studies, nine met inclusion criteria, representing a range of psychological, pharmaceutical, and other interventions and outcome measures. Meta-analytic methods were not feasible because of the serious risk of bias in all studies, and results were therefore synthesized narratively. There is limited and low-quality evidence of the effects of a variety of interventions to improve the sleep quality of people living with PD. Further research might consider specifically including people diagnosed with PD in trials of sleep interventions and using sleep outcome measures in trials of established PD treatments.

Sleep Quality After Quetiapine Augmentation in Patients With Treatment-Resistant Depression and Personality Disorders.

PURPOSE/BACKGROUND: Quetiapine is a first-line augmenting agent for treatment-resistant depression (TRD) and is used off-label in insomnia. Quetiapine and its active metabolite norquetiapine act mostly on 5-HT2A, 5-HT2C, H1, and D2 as antagonists and on 5-HT1A as partial agonists. Patients with TRD often have comorbid personality disorder (PD), and evidence suggests an association between sleep disturbance and recovery among patients with PD. Here, we aimed to evaluate the effects of quetiapine on sleep in TRD patients with and without PD (PD+/PD-). METHODS/PROCEDURES: We reviewed health records of 38 patients with TRD (20 TRD/PD+) who had been treated with a pharmacotherapy regimen including quetiapine. Clinical outcomes were determined by comparing changes in sleep items of the Hamilton Depression Rating Scale at the beginning (T0) and after 3 months of an unchanged treatment (T3). FINDINGS/RESULTS: Patients with TRD/PD+ and TRD/PD- taking quetiapine showed significant improvement in sleep items from T0 to T3 (P < 0.001, ηp2 ≥ 0.19). There was a significant personality × time interaction for sleep-maintenance insomnia (P = 0.006, ηp2 = 0.23), with TRD/PD+ showing a greater improvement at T3 compared with TRD/PD- (P = 0.01). While exploring other sleep items, no personality × time interaction was found. In the TRD/PD- group, improvement in sleep items was associated with an overall improvement in depressive symptoms (r = 0.55, P = 0.02). IMPLICATIONS/CONCLUSIONS: Quetiapine induced greater improvements in sleep-maintenance insomnia among TRD/PD+ patients than TRD/PD-. These findings suggest quetiapine could have a therapeutic role for insomnia in PD underscoring a distinct underlying neurobiological mechanism of sleep disturbance in people living with PD.

The association of severe COVID anxiety with poor social functioning, quality of life, and protective behaviours among adults in United Kingdom: a cross-sectional study.

BACKGROUND: Anxiety about COVID-19 is common. For most people this is an appropriate response to the loss of livelihoods and loved-ones, disruptions to social networks, and uncertainty about the future. However, for others these anxieties relate to contracting the virus itself, a phenomenon termed COVID anxiety. Little is known about the characteristics of people with severe COVID anxiety or the impact it has on their daily lives. METHODS: We conducted a two-phase cross-sectional survey of people aged 18 or over who were living in United Kingdom, self-identified as anxious about COVID-19, and had a score of ≥9 on the Coronavirus Anxiety Scale. We recruited participants nationally through online adverts and locally via primary care services in London. Data on demographic and clinical factors were used in multiple regression modelling to examine the greatest contributors to functional impairment, poor health-related quality of life and protective behaviours in this sample of individuals with severe COVID anxiety. RESULTS: We recruited 306 people with severe COVID anxiety between January and September 2021. Most were female (n = 246, 81.2%); they had a median age of 41 (range = 18-83). The majority of participants also had generalised anxiety (n = 270, 91.5%), depression (n = 247, 85.5%), and a quarter (n = 79, 26.3%) reported a physical health condition which put them at increased risk of hospitalisation with COVID-19. Half had severe social dysfunction (n = 151, 52.4%). One in ten reported never leaving their home, one in three washed all items brought into their house, one in five washed their hands constantly, and one in five of those with children reported not sending them to school because of fears of COVID-19. Increasing co-morbid depressive symptoms best explained functional impairment and poor quality of life after controlling for other factors. CONCLUSIONS: This study highlights the high degree of co-occuring mental health problems, and the extent of functional impairment and poor health-related quality of life among people with severe COVID anxiety. Further research is needed to establish the course of severe COVID anxiety as the pandemic progresses, and steps that can be taken to support people who experience this distress.

Air pollution and mental health: associations, mechanisms and methods.

PURPOSE OF REVIEW: There is increasing interest in the links between exposure to air pollution and a range of health outcomes. The association with mental health however is much less established. This article reviews developments in the field over the past 12 months, highlighting the evidence for causation, associations between multiple air pollutants and mental health outcomes, and assesses the challenges of researching this topic. RECENT FINDINGS: Increasingly rigorous methods are being applied to the investigation of a broader range of mental health outcomes. These methods include basic science, neuroimaging, and observational studies representing diverse geographical locations. Cohort studies with linked high-resolution air pollutant exposure data are common, facilitating advanced analytic methods. To date, meta-analyses have demonstrated small and significant positive associations between long-term exposure to fine particulate matter and depressive symptoms and cognitive decline. Methodological complexities in measuring exposure and outcome pose ongoing difficulties for the field. SUMMARY: Literature on this topic has recently seen an appreciable expansion. Work that better estimates daily exposure, controls for complex confounders, and is driven by hypotheses founded in candidate causal mechanisms would help clarify associations, and inform targeted interventions and policymakers.

Infection control and the prevalence, management and outcomes of SARS-CoV-2 infections in mental health wards in London, UK: lessons learned from wave 1 to wave 2.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has high morbidity and mortality in older adults and people with dementia. Infection control and prevention measures potentially reduce transmission within hospitals. AIMS: We aimed to replicate our earlier study of London mental health in-patients to examine changes in clinical guidance and practice and associated COVID-19 prevalence and outcomes between COVID-19 waves 1 and 2 (1 March to 30 April 2020 and 14 December 2020 to 15 February 2021). METHOD: We collected the 2 month period prevalence of wave 2 of COVID-19 in older (≥65 years) in-patients and those with dementia, as well as patients' characteristics, management and outcomes, including vaccinations. We compared these results with those of our wave 1 study. RESULTS: Sites reported that routine testing and personal protective equipment were available, and routine patient isolation on admission occurred throughout wave 2. COVID-19 infection occurred in 91/358 (25%; 95% CI 21-30%) v. 131/344, (38%; 95% CI 33-43%) P < 0.001 in wave 1. Hospitals identified more asymptomatic carriers (26/91; 29% v. 16/130; 12%) and fewer deaths (12/91; 13% v. 19/131; 15%; odds ratio = 0.92; 0.37-1.81) compared with wave 1. The patient vaccination uptake rate was 49/58 (85%). CONCLUSIONS: Patients in psychiatric in-patient settings, mostly admitted without known SARS-CoV-2 infection, had a high risk of infection compared with people in the community but lower than that during wave 1. Availability of infection control measures in line with a policy of parity of esteem between mental and physical health appears to have lowered within-hospital COVID-19 infections and deaths. Cautious management of vulnerable patient groups including mental health patients may reduce the future impact of COVID-19.

Severe COVID-19 anxiety among adults in the UK: protocol for a cohort study and nested feasibility trial of modified cognitive-behavioural therapy for health anxiety.

INTRODUCTION: Some people are so anxious about COVID-19 that it impairs their functioning. However, little is known about the course of severe COVID-19 anxiety or what can be done to help people who experience it. METHODS AND ANALYSIS: Cohort study with a nested feasibility trial with follow-up at 3 and 6 months. We recruited 306 people who were aged 18 and over, lived in the UK and had severe COVID-19 anxiety (indicated by a score of 9 or more on the Coronavirus Anxiety Scale (CAS)). To take part in the nested feasibility trial, participants also had to have a score of 20 or more on the Short Health Anxiety Inventory. We excluded people from the trial if they had had COVID-19 within the previous 4 weeks, if they were currently self-isolating or if they were already receiving psychological treatment.We publicised the study nationally through adverts, social media and posts on message boards. We also recruited participants via clinicians working in primary and secondary care NHS services in London. All those in the active arm will be offered 5-10 sessions of remotely delivered modified cognitive-behavioural therapy for health anxiety (CBT-HA). We will examine the proportion of participants who remain above threshold on the CAS at 3 and 6 months and factors that influence levels of COVID-19 anxiety over 6 months using mixed effects logistic regression. The key feasibility metrics for the nested trial are the level of uptake of CBT-HA and the rate of follow-up. ETHICS AND DISSEMINATION: Approved by Leicester Central Research Ethics Committee (reference: 20/EM/0238). The results of the study will be published in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: ISRCTN14973494.

Adrenergic receptor modulation of hippocampal CA3 network activity.

Norepinephrine (NE) has demonstrated proconvulsant and antiepileptic properties; however, the specific pharmacology of these actions has not been clearly established. To address this, we studied the effect of NE on hippocampal CA3 epileptiform activity. Frequency changes of burst discharges in response to NE were biphasic; low concentrations increased the number of bursts, while higher concentrations reduced their frequency, suggesting the involvement of multiple adrenergic receptor (AR) types. This hypothesis was confirmed when, in the presence of betaAR blockade, increasing concentrations of NE caused a monophasic decrease in epileptiform activity. Antagonists selective for alpha1 or alpha2ARs were then used to determine which alphaAR type was involved. While discriminating concentrations of the alpha1AR antagonists prazosin and terazosin had no effect, selective amounts of the alpha2AR antagonists RS79948 and RX821002 significantly reduced the potency of NE in decreasing epileptiform activity. Furthermore, this antiepileptic action of NE persisted when all GABA-mediated inhibition was blocked. This data suggests that, under conditions of impaired GABAergic inhibition, the excitatory and inhibitory effects of NE on hippocampal CA3 epileptiform activity are mediated primarily via beta and alpha2ARs, respectively. Moreover, our results imply that the antiepileptic effect of alpha2AR activation in CA3 is not dependent on the GABAergic system.

Beta1 adrenergic receptor-mediated enhancement of hippocampal CA3 network activity.

Norepinephrine is an endogenous neurotransmitter distributed throughout the mammalian brain. In higher cortical structures such as the hippocampus, norepinephrine, via beta adrenergic receptor (AR) activation, has been shown to reinforce the cognitive processes of attention and memory. In this study, we investigated the effect of beta1AR activation on hippocampal cornu ammonis 3 (CA3) network activity. AR expression was first determined using immunocytochemistry with antibodies against beta1ARs, which were found to be exceptionally dense in hippocampal CA3 pyramidal neurons. CA3 network activity was then examined in vitro using field potential recordings in rat brain slices. The selective betaAR agonist isoproterenol caused an enhancement of hippocampal CA3 network activity, as measured by an increase in frequency of spontaneous burst discharges recorded in the CA3 region. In the presence of alphaAR blockade, concentration-response curves for isoproterenol, norepinephrine, and epinephrine suggested that a beta1AR was involved in this response, and the rank order of potency was isoproterenol > norepinephrine = epinephrine. Finally, equilibrium dissociation constants (pK(b)) of subtype-selective betaAR antagonists were functionally determined to characterize the AR subtype modulating hippocampal CA3 activity. The selective beta1AR antagonists atenolol and metoprolol blocked isoproterenol-induced enhancement, with apparent K(b) values of 85 +/- 36 and 3.9 +/- 1.7 nM, respectively. In contrast, the selective beta2AR antagonists ICI-118,551 and butoxamine inhibited isoproterenol-mediated enhancement with apparent low affinities (K(b) of 222 +/- 61 and 9268 +/- 512 nM, respectively). Together, this pharmacological profile of subtype-selective betaAR antagonists indicates that in this model, beta1AR activation is responsible for the enhanced hippocampal CA3 network activity initiated by isoproterenol.