The aims of this study were to evaluate the literature regarding the use of ultra-low-field magnetic resonance imaging (ULF-MRI) and its potential use in dementia diagnosis.

Access to neuroimaging causes bottlenecks in dementia diagnostic pathways and limits overall capacity; there is wide variation across the UK. At present, dementia diagnosis rates in the UK remain below 65% and significant improvements in efficiency and accessibility of assessment services are needed to meet growing demand.

Modern MRI scanners use high strength magnetic fields (typically 1.5–3T), are expensive to install and operate, and usually require patients to travel to a general hospital. ULF-MRI systems (typically < 0.1T) are portable, relatively inexpensive, and do not require specialist staff to operate. They do not require shielding and are powered via a standard electrical socket. The use of ULF-MRI has historically been limited by multiple factors including poor image quality. Advances in software and hardware now mean that there is realistic potential to use ULF-MRI across a range of clinical applications.

The study followed the PRISMA 2020 guidelines and was registered on PROSPERO. Five electronic databases were searched for studies related to ULF-MRI using pre-developed terms. Studies comparing high field and ULF-MRI neuroimaging in adults were included. Studies of acute presentations (e.g. traumatic brain injury or acute cerebrovascular accident) were excluded. A data extraction template was used to synthesise study characteristics and outcomes. Two reviewers completed the selection process and data extraction independently.

2357 citations were identified, from which 101 studies were selected for further review based on title and abstract, of which eight met criteria for inclusion. Further studies were identified by forward and backward citation searching and through contact with active researchers in the field. The selected publications included both single and multi-centre studies. The Hyperfine Swoop system was used in almost all studies. Mean participant age range was 31 to 63. Qualitative and quantitative comparisons demonstrated good correspondence between high field and ULF-MRI across a range of measures studied, including volumetric measures and moderate to severe white matter hyperintensities.

The limited available evidence suggests that there is potential for ULF-MRI to transform the approach to neuroimaging in the assessment of dementia. Dedicated research into the use of ULF-MRI in this specific application will determine if it will be one of the much-needed disruptors to our current processes of dementia assessment.

Non epileptic attacks (also referred to as psychogenic non-epileptic seizures, functional seizures or dissociative seizures) are similar in appearance to epileptic seizures but are not accompanied by ictal electroencephalographic (EEG) discharges. NEAD is classified as either a conversion or dissociative disorder in DSM-V and ICD11 respectively, and is often associated with significant long-term disability. People with NEAD often access care across many different specialties and healthcare settings. Their experiences of doing so are frequently negative, based both on interactions with clinicians and integration of care.

The aims of this study were to review the existing literature on the attitudes of clinicians towards non-epileptic attack disorder (NEAD), and any differences that exist between professional groups.

The study followed PRISMA 2020 guidelines and was registered on the international prospective register of systematic reviews (PROSPERO). Three electronic databases (MEDLINE, EMBASE and PsycInfo) were searched for studies of clinician attitudes towards NEAD using pre-developed terms. These terms were optimised following familiarisation with the literature. Specific inclusion and exclusion criteria were applied, and studies were selected if they included data regarding the attitudes of healthcare professionals from any group towards NEAD. A data extraction template was used to synthesise study characteristics and outcomes. The Mixed Methods Appraisal Tool was used to appraise methodological quality of the included studies. Two reviewers independently completed the selection process and data extraction.

The search strategy yielded 2885 citations, of which 76 were selected for review of the full publication based on the title and abstract. Inclusion/exclusion criteria were applied to full texts. The literature mainly included clinicians from general practice, neurology, emergency department and psychiatry. There was general negative stereotyping of people with NEAD and a lack of confidence in management. Attitudes differed between professions, particularly with respect to aetiology.

The literature highlighted that many clinicians held a negative attitude towards people with NEAD, and there was evidence of a general lack in confidence towards NEAD across all healthcare professional groups. There was a difference between healthcare professional groups, mostly related to views on aetiology. The review highlights the need for greater education related to NEAD with a focus on understanding aetiology and greater transparency in interdisciplinary working.

Digital Mental Health Interventions (DMHIs) that meet the definition of a medical device are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The MHRA uses procedures that were originally developed for pharmaceuticals to assess the safety of DMHIs. There is recognition that this may not be ideal, as is evident by an ongoing consultation for reform led by the MHRA and the National Institute for Health and Care Excellence.

The aim of this study was to generate an experts’ consensus on how the medical regulatory method used for assessing safety could best be adapted for DMHIs.

An online Delphi study containing three rounds was conducted with an international panel of 20 experts with experience/knowledge in the field of UK digital mental health.

Sixty-four items were generated, of which 41 achieved consensus (64%). Consensus emerged around ten recommendations, falling into five main themes: Enhancing the quality of adverse events data in DMHIs; Re-defining serious adverse events for DMHIs; Reassessing short-term symptom deterioration in psychological interventions as a therapeutic risk; Maximising the benefit of the Yellow Card Scheme; and Developing a harmonised approach for assessing the safety of psychological interventions in general.

The implementation of the recommendations provided by this consensus could improve the assessment of safety of DMHIs, making them more effective in detecting and mitigating risk.

Weight gain, cardiometabolic complications and psychosis are implicated in significant reduction in life expectancy.While there is current research to uncover a shared aetiology for mental illness and metabolic diseases, people with FEP are especially vulnerable to rapid weight gain during the early stages of treatment due to the side effects profile of many antipsychotic medications. Physical exercise along with lifestyle and dietary modifications have proven efficacy in weight reduction, improving metabolic profile and mental well-being and may be valuable interventions during the early stages of a psychotic illness.Our aim was to find evidence to support the use of non-pharmacological interventions in managing weight gain in people with FEP.

We conducted a systematic review of electronic databases; MEDLINE, EMBASE and PsycINFO on 06/01/2023. We included all studies that looked at non-pharmacological interventions in the management of weight gain for people diagnosed with FEP. Findings are reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two authors independently assessed the included studies’ methodological quality using The National Institute of Health (NIH) quality assessment tool for cohort and cross-sectional studies and all included studies were rated as good.

Our search identified 221 studies and 5 met our inclusion criteria. All studies had a control group that received treatment as usual (TAU) and a test group with Interventions such as dietetic support and exercise programs. Four of the studies demonstrated reduced weight gain on follow up with lifestyle interventions that were statistically significant while the remaining one study did not show a significant difference between groups. One study showed sustained improvement in diet quality with no significant weight change at 2 year follow up. The essential lifestyle interventions that led to reduced weight gain included psychoeducation on healthy lifestyle, dietary modifications and exercise.

Three studies included cardiovascular risk factors such as lipid profile and blood glucose. One of them demonstrated increased cardiometabolic risk factors at baseline which worsened initially but improved after 1 to 2 years of intervention. Another study found increased cholesterol in the intervention group and increased glucose levels in the TAU group and the third study did not find a significant difference between the groups.

Lifestyle weight-management interventions have the potential to reduce weight gain in patients with FEP receiving antipsychotic treatment, but research evidence is very limited at present.

Transcranial Magnetic Stimulation (TMS) is an in-vivo, non-invasive, and safe method that probes neurophysiological properties associated with cortical glutamatergic (excitatory) and GABAergic (inhibitory) neurotransmission. The combination of TMS with Electroencephalography (EEG) allows us to measure TMS-evoked cortical responses directly from brain activity and it is uniquely placed to elucidate in-vivo cortical Excitatory/Inhibitory processes. Schizophrenia has been associated with Excitation/Inhibition (E/I) imbalance. Cognitive impairment, which is almost ubiquitous in schizophrenia, has been linked with the E/I abnormalities observed in schizophrenia. Among the TMS-EEG evoked potentials (TEPs), the N100 is thought to reflect activation of inhibitory GABA-B cortical circuits and has been associated with attentional processes in healthy individuals, attention deficit hyperactivity disorder (ADHD) and depression. Our aim was to investigate the cortical processes related to the generation of N100 after motor cortex stimulation and its association with attention measures in patients with schizophrenia and healthy controls.

TEPs were recorded following application of 150 TMS pulses at 90% of resting motor threshold on two brain sites, i.e., left primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) in stable patients with schizophrenia (n = 9) and healthy controls (n = 9). Region of Interest (ROI) analysis was performed to calculate the regional average of the N100 peak amplitude in M1 and DLPFC based on previous literature. Attention was assessed with a Continuous Performance Task (CPT).

We found a significant negative correlation between the amplitude of N100 from M1 and CPT score in the patient group (rho = -0.73, p = 0.026). The N100 component from DLPFC in patients did not correlate with the CPT score (rho = -0.034, p = 0.93), which may suggest regional specificity of M1 inhibitory processes in attention in patients with schizophrenia.

N100 is considered to be related to cortical inhibitory processes influenced by cortico–striato–thalamo–cortical loops, with greater cortical inhibitory activity producing a larger N100 amplitude. Our preliminary results suggest association of the GABA-B-ergic TEP N100 with attentional processes in M1 and may represent cortical inhibition beyond motor inhibition in patients with schizophrenia. Overall, TMS-EEG offers the potential to investigate the state and dynamics of E/I imbalance in schizophrenia and cognition.

Clozapine is licensed for treatment-resistant psychosis and remains underutilised. This may berelated to the stringent haematological monitoring requirements that are mandatory in most countries. We aimed to compare guidelines internationally and develop a novel Stringency Index. We hypothesised that the most stringent countries would have increased healthcare costs and reduced prescription rates.

We conducted a literature review and survey of guidelines internationally. Guideline identification involved a literature review and consultation with clinical academics. We focused on the haematological monitoring parameters, frequency and thresholds for discontinuation and rechallenge after suspected clozapine-induced neutropenia. In addition, indicators reflecting monitoring guideline stringency were scored and visualised using a choropleth map. We developed a Stringency Index with an international panel of clozapine experts, through a modified-Delphi-survey. The Stringency Index was compared to health expenditure per-capita and clozapine prescription per 100 000 persons.

One hundred twocountries were included, from Europe (n = 35), Asia (n = 24), Africa (n = 20), South America (n = 11), North America (n = 7) and Oceania and Australia (n = 5). Guidelines differed in frequency of haematological monitoring and discontinuation thresholds. Overall, 5% of included countries had explicit guidelines for clozapine-rechallenge and 40% explicitly prohibited clozapine-rechallenge. Furthermore, 7% of included countries had modified discontinuation thresholds for benign ethnic neutropenia. None of the guidelines specified how long haematological monitoring should continue. The most stringent guidelines were in Europe, and the least stringent were in Africa and South America. There was a positive association (r = 0.43, p < 0.001) between a country's Stringency Index and healthcare expenditure per capita.

Recommendations on how haematological function should be monitored in patients treated with clozapine vary considerably between countries. It would be useful to standardise guidelines on haematological monitoring worldwide.

Given psychotic illnesses' high heritability and associations with brain structure, numerous neuroimaging-genetics findings have been reported in the last two decades. However, few findings have been replicated. In the present independent sample we aimed to replicate any psychosis-implicated SNPs (single nucleotide polymorphisms), which had previously shown at least two main effects on brain volume.

A systematic review for SNPs showing a replicated effect on brain volume yielded 25 studies implicating seven SNPs in five genes. Their effect was then tested in 113 subjects with either schizophrenia, bipolar disorder, ‘at risk mental state’ or healthy state, for whole-brain and region-of-interest (ROI) associations with grey and white matter volume changes, using voxel-based morphometry.

We found FWER-corrected (Family-wise error rate) (i.e. statistically significant) associations of: (1) CACNA1C-rs769087-A with larger bilateral hippocampus and thalamus white matter, across the whole brain; and (2) CACNA1C-rs769087-A with larger superior frontal gyrus, as ROI. Higher replication concordance with existing literature was found, in decreasing order, for: (1) CACNA1C-rs769087-A, with larger dorsolateral-prefrontal/superior frontal gyrus and hippocampi (both with anatomical and directional concordance); (2) ZNF804A-rs11681373-A, with smaller angular gyrus grey matter and rectus gyri white matter (both with anatomical and directional concordance); and (3) BDNF-rs6265-T with superior frontal and middle cingulate gyri volume change (with anatomical and allelic concordance).

Most literature findings were not herein replicated. Nevertheless, high degree/likelihood of replication was found for two genome-wide association studies- and one candidate-implicated SNPs, supporting their involvement in psychosis and brain structure.

Conventional pharmacological approaches have limited effectiveness for schizophrenia. There is interest in the application of oxytocin, which is involved in social cognition. Clinical trials have yielded mixed results, with a gap in understanding neural mechanisms.

To evaluate the behavioural impact of oxytocin administration on a social learning task in individuals with schizophrenia, and elucidate any differential neural activity produced.

We recruited 20 clinically stable right-handed men diagnosed with schizophrenia or schizoaffective disorder. In a double-blind cross-over randomised controlled study, 40 IU of oxytocin or placebo were administered before functional magnetic resonance imaging of participants playing a multi-round economic exchange game of trust. Participants had the role of investors (investment trials) receiving repayment on their investments (repayment trials), playing one session against a computer and a second against a player believed to be human.

During investment trials, oxytocin increased neural signalling in the right lateral parietal cortex for both human and computer player trials, and attenuated signalling in the right insula for human player trials. For repayment trials, oxytocin elicited signal increases in left insula and left ventral caudate, and a signal decrease in right amygdala during the human player trials; conversely it resulted in right dorsal caudate activation during the computer player trials. We did not find a significant change in behavioural performance associated with oxytocin administration, or any associations with symptoms.

During a social learning task oxytocin modulates cortical and limbic substrates of the reward-processing network. These perturbations can be putatively linked to the pathoaetiology of schizophrenia.

COVID-19 causes cognitive, neurophysical and psychiatric sequalae that persist beyond the acute illness. These appear to be independent of the direct impact on respiratory function although the impact of multiorgan, especially brain pathology, may be a contributory factor – as may psycho-social effects of the disease. We performed a systematic review of literature to assess the sequelae of post-acute COVID-19 syndrome to better understand the need for dedicated interventions to improve functioning.

We conducted a systematic review of reports included in MEDLINE, PsycINFO, and EMBASE. We searched for cohort studies exploring psychiatric and neuro-cognitive sequelae of post-acute COVID-19 in adults with a sample size of at least 100. The search was conducted on 4 February 2022. Findings are reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two authors independently assessed the included studies’ methodological quality using The National Institute of Health (NIH) quality assessment tool for observational cohort and cross-sectional studies and all records were rated as good or fair.

Our search identified 66 records and 14 met protocol requirements. The studies varied in sample size ranging from 100 to 3762 participants. Time to follow-up ranged from 1–12 months. Main symptoms identified by a majority of the studies were; Fatigue (25% to 85%) and Sleep problems (20% to 79%). Psychiatric symptoms; Anxiety (19% to 56%), Depression (11% to 47%), PTSD (6% to 43%) and altered sense of reality (3% to 15%). Neuro-cognitive symptoms; Cognitive dysfunction (25% to 85%), brain fog (12% to 81%), memory problems (24% to 73%), concentration difficulties (25% to 54%), and attention deficit (27%).

Female sex, advanced age, pre-morbid asthma or COPD, increased disease severity, high BMI and new neurological complications during hospitalisation were some of the identified risk factors for persistent symptoms in post-acute COVID-19. One study identified male sex as a risk factor for moderate to severe PTSD. Current evidence suggests that symptoms decrease over time.

There is clear evidence of neuro-physical, psychiatric and neurocognitive sequelae in post-acute COVID-19 syndrome. Differences in assessing and reporting findings makes it difficult to synthesize meaningful information. Identifying and formulating standardised assessments for outcome measures and reporting systems would be useful in future research. Further research into symptoms of post-acute COVID-19, to understand the pathophysiology will better enable us to raise public awareness, introduce preventative measures and incorporate appropriate treatment strategies for rehabilitation.

Treatment-resistant schizophrenia is a major disabling illness which often proves challenging to manage in a secondary care setting. The National Psychosis Unit (NPU) is a specialised tertiary in-patient facility that provides evidence-based, personalised, multidisciplinary interventions for complex treatment-resistant psychosis, in order to reduce the risk of readmission and long-term care costs.

This study aimed to assess the long-term effectiveness of treatment at the NPU by considering naturalistic outcome measures.

Using a mirror image design, we compared the numbers of psychiatric and general hospital admissions, in-patient days, acuity of placement, number of psychotropic medications and dose of antipsychotic medication prescribed before and following NPU admission. Data were obtained from the Clinical Records Interactive Search system, an anonymised database sourced from the South London and Maudsley NHS Trust electronic records, and by means of anonymous linkage to the Hospital Episode Statistics system.

Compared with the 2 years before NPU admission, patients had fewer mental health admissions (1.65 ± 1.44 v. 0.87 ± 0.99, z = 5.594, P < 0.0001) and less mental health bed usage (335.31 ± 272.67 v. 199.42 ± 261.96, z = 5.195 P < 0.0001) after NPU admission. Total in-patient days in physical health hospitals and total number of in-patient days were also significantly reduced (16.51 ± 85.77 v. 2.83 ± 17.38, z = 2.046, P = 0.0408; 351.82 ± 269.09 v. 202.25 ± 261.05, z = 5.621, P < 0.0001). The reduction in level of support required after treatment at the NPU was statistically significant (z = −8.099, P < 0.0001).

This study demonstrates the long-term effectiveness of a tertiary service specialising in treatment-resistant psychosis.

Clozapine is uniquely effective in treatment-resistant psychosis but remains underutilised, partly owing to psychotic symptoms leading to non-adherence to oral medication. An intramuscular formulation is available in the UK but outcomes remain unexplored.

This was a retrospective clinical effectiveness study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis over a 3-year period.

Successful initiation of oral clozapine after intramuscular prescription was the primary outcome. Secondary outcomes included all-cause clozapine discontinuation 2 years following initiation, and 1 year after discharge. Discontinuation rates were compared with a cohort prescribed only oral clozapine. Propensity scores were used to address confounding by indication.

Among 39 patients prescribed intramuscular clozapine, 19 received at least one injection, whereas 20 accepted oral clozapine when given an enforced choice between the two. Thirty-six (92%) patients successfully initiated oral clozapine after intramuscular prescription; three never transitioned to oral. Eight discontinued oral clozapine during the 2-year follow-up, compared with 83 out of 162 in the comparator group (discontinuation rates of 24% and 50%, respectively). Discontinuation rates at 1-year post-discharge were 21%, compared with 44% in the comparison group. Intramuscular clozapine prescription was associated with a non-significantly lower hazard of discontinuation 2 years after initiation (hazard ratio 0.39, 95% CI 0.14–1.06) and 1 year after discharge (hazard ratio 0.37, 95% CI 0.11–1.24). The only reported adverse event specific to the intramuscular formulation was injection site pain and swelling.

Intramuscular clozapine prescription allowed transition to oral maintenance in an initially non-adherent cohort. Discontinuation rates were similar to patients only prescribed oral clozapine and comparable to existing literature.

After reading this article you will be able to:

• • understand the relative incidence of cardiotoxic side-effects of the various SGAs

• • perform preliminary investigations to diagnose the common cardiotoxic side-effects of SGAs

• • understand the treatments for these cardiac side-effects and the role of cardiologists involved the care of these patients.

‘Rebound’ or ‘withdrawal’ symptoms are frequently observed after a sudden discontinuation of clozapine. We describe a patient with treatment-resistant schizoaffective disorder who developed agranulocytosis on clozapine but was successfully switched to treatment with olanzapine with no deterioration in her condition. We put forward three possible theories which may have accounted for the lack of rebound symptoms in this patient: the pharmacological profile of olanzapine, the anticholinergic effects of hyoscine hydrobromide, and the possibility that this patient may not be treatment-resistant and so have a reduced risk of rebound psychosis due to displaying a different pathophysiology.

None.