Who was Heather Ashton?

Introduction

Heather Ashton FRCP (11 July 1929 to 15 September 2019) was a British psychopharmacologist and physician. She is best known for her clinical and research work on benzodiazepene dependence.

Biography

Chrystal Heather Champion was born in Dehradun, northern India, to Harry Champion, a British silviculturalist, and Chrystal (Parsons) Champion, a secretary. From the age of six, she attended a boarding school in Swanage, Dorset, England. When WWII began, she was evacuated to West Chester, Pennsylvania; during the crossing, her ship was attacked by a U-boat.

Ashton went on to study Medicine at Somerville College, Oxford, graduating with a First Class Honours Degree (BA) in Physiology in 1951. She earned her medical degree (DM) in 1956. She completed professional training at Middlesex Hospital. She was elected as a Fellow of the Royal College of Physicians, London, in 1975.

In 1965, Ashton joined the faculty at Newcastle University, first in the Department of Pharmacology and later in the Department of Psychiatry. From 1982 to 1994, she ran a benzodiazepine withdrawal clinic at the Royal Victoria Infirmary in Newcastle. She was on the executive committee of the North East Council on Addictions. Ashton also helped set up the British organisation Victims of Tranquillisers (VOT). She also gave evidence to British government committees on tobacco smoking, cannabis and benzodiazepines.

Ashton died on 15 September 2019 at her home in Newcastle upon Tyne, at age 90.

Research

Ashton’s developed her expertise in the effects of psychoactive drugs and the effects of substances such as nicotine and cannabis on the brain.

During the 1960s, benzodiazepines, like diazepam and temazepam, had become popular and were seen as safe and effective treatments for anxiety or insomnia. One study found that the overdose death rate among patients taking both benzodiazepines and opioids was 10 times higher than among those who only took opioids.

Ashton’s research on these drugs found that they could be used in the short term, but could lead to physical dependence over the long-term. She also recognised that this benzodiazepine withdrawal syndrome was very different from those addicted to illegal drugs. This led to her writing an important manual to help those who were trying to stop their prescribed benzodiazepine. This manual is now used all over the world. This book, Benzodiazepines: How They Work and How to Withdraw, was first published in 1999; it has become known as the Ashton Manual and has been translated into 11 languages. Ashton’s research was influential, leading to changes in prescribing practices and guidelines recommended for benzodiazepines in 2013. Her research on psychotropic drugs led to over 200 journal articles, chapters and books, including over 50 papers concerning benzodiazepines alone.

Is there an Association between Metabolic Disorder & Cognitive Impairment in Patients with Early-Stage Schizophrenia?

Research Paper Title

The Association Between Metabolic Disturbance and Cognitive Impairments in Early-Stage Schizophrenia.

Background

Cognitive impairment is one of the core symptoms of schizophrenia, which is considered to be significantly correlated to prognosis. In recent years, many studies have suggested that metabolic disorders could be related to a higher risk of cognitive defects in a general setting. However, there has been limited evidence on the association between metabolism and cognitive function in patients with early-stage schizophrenia.

Methods

In this study, the researchers recruited 172 patients with early-stage schizophrenia. Relevant metabolic parameters were examined and cognitive function was evaluated by using the MATRICS Consensus Cognitive Battery (MCCB) to investigate the relationship between metabolic disorder and cognitive impairment.

Results

Generally, the prevalence of cognitive impairment among patients in our study was 84.7% (144/170), which was much higher than that in the general population. Compared with the general Chinese setting, the study population presented a higher proportion of metabolic disturbance. Patients who had metabolic disturbance showed no significant differences on cognitive function compared with the other patients. Correlation analysis showed that metabolic status was significantly correlated with cognitive function as assessed by the cognitive domain scores (p < 0.05), while such association was not found in further multiple regression analysis.

Conclusions

Therefore, there may be no association between metabolic disorder and cognitive impairment in patients with early-stage schizophrenia.

Reference

Peng, X-J., Hei, G-R., Li, R-R., Yang, Y., Liu, C-C., Xiao, J-M., Long, Y-J., Shao, P., Huang, J., Zhao, J-P. & Wu, R-R. (2021) The Association Between Metabolic Disturbance and Cognitive Impairments in Early-Stage Schizophrenia. Frontiers in Human Neuroscience. doi: 10.3389/fnhum.2020.599720. eCollection 2020.

Developing a Longitudinal Trajectory-Based Approach to Investigating Relapse Trend Differences in Mental Health Patients

Research Paper Title

Differences in Temporal Relapse Characteristics Between Affective and Non-affective Psychotic Disorders: Longitudinal Analysis.

Background

Multiple relapses over time are common in both affective and non-affective psychotic disorders. Characterizing the temporal nature of these relapses may be crucial to understanding the underlying neurobiology of relapse.

Methods

Anonymised records of patients with affective and non-affective psychotic disorders were collected from SA Mental Health Data Universe and retrospectively analysed. To characterise the temporal characteristic of their relapses, a relapse trend score was computed using a symbolic series-based approach. A higher score suggests that relapse follows a trend and a lower score suggests relapses are random. Regression models were built to investigate if this score was significantly different between affective and non-affective psychotic disorders.

Results

Logistic regression models showed a significant group difference in relapse trend score between the patient groups. For example, in patients who were hospitalized six or more times, relapse score in affective disorders were 2.6 times higher than non-affective psychotic disorders [OR 2.6, 95% CI (1.8-3.7), p < 0.001].

Discussion

The results imply that the odds of a patient with affective disorder exhibiting a predictable trend in time to relapse were much higher than a patient with recurrent non-affective psychotic disorder. In other words, within recurrent non-affective psychosis group, time to relapse is random.

Conclusions

This study is an initial attempt to develop a longitudinal trajectory-based approach to investigate relapse trend differences in mental health patients. Further investigations using this approach may reflect differences in underlying biological processes between illnesses.

Reference

Immanuel, S.A., Schrader, G. & Bidargaddi, N. (2021) Differences in Temporal Relapse Characteristics Between Affective and Non-affective Psychotic Disorders: Longitudinal Analysis. Frontiers in Psychiatry. doi: 10.3389/fpsyt.2021.558056. eCollection 2021.

Can Lorazepam be Considered to be a Clinically Effective Means of Treating the Acutely Agitated Patient?

Research Paper Title

Treatment of Agitation With Lorazepam in Clinical Practice: A Systematic Review.

Background

Acute agitation is a frequent occurrence in both inpatient and outpatient psychiatric settings, and the use of medication to calm a patient may be warranted to mitigate the situation. Lorazepam is a benzodiazepine that is widely used for management of acute agitation. Despite its widespread use, there is remarkably little clinical evidence for the benefits of lorazepam in acute agitation.

Methods

The researchers performed a systematic review with focus on lorazepam, including all randomised clinical trials on lorazepam in mental and behavioural disorders, excluding studies on dementia and paediatric patients and in mixed conditions.

Results

A total of 11 studies met inclusion criteria, and all were in patients with mental and behavioural disorders. Most trials generally found improvements across a variety of outcomes related to agitation, although there was some disparity if specific outcomes were considered.

In the five studies with haloperidol, the combination of lorazepam and haloperidol was superior to either agent alone, but with no differences between monotherapy with the individual agents.

Conclusions

In the study comparing lorazepam to olanzapine, olanzapine was superior to lorazepam, and both were superior to placebo.

As expected, the safety of lorazepam among the different studies was consistent with its well-characterised profile with dizziness, sedation, and somnolence being the most common adverse events.

Based on this structured review, lorazepam can be considered to be a clinically effective means of treating the acutely agitated patient.

Reference

Amore, M., D’Andrea, M. & Fagiolini, F. (2021) Treatment of Agitation With Lorazepam in Clinical Practice: A Systematic Review.

Can the MHS: A Serve as a Clinically Useful Screening Tool for GAD?

Research Paper Title

A Brief Online and Offline (Paper-and-Pencil) Screening Tool for Generalized Anxiety Disorder: The Final Phase in the Development and Validation of the Mental Health Screening Tool for Anxiety Disorders (MHS: A).

Background

Generalised anxiety disorder (GAD) can cause significant socioeconomic burden and daily life dysfunction; hence, therapeutic intervention through early detection is important.

Methods

This study was the final stage of a 3-year anxiety screening tool development project that evaluated the psychometric properties and diagnostic screening utility of the Mental Health Screening Tool for Anxiety Disorders (MHS: A), which measures GAD.

Results

A total of 527 Koreans completed online and offline (i.e., paper-and pencil) versions of the MHS: A, Beck Anxiety Inventory (BAI), Generalised Anxiety Disorder-7 (GAD-7), and Penn State Worry Questionnaire (PSWQ). The participants had an average age of 38.6 years and included 340 (64.5%) females. Participants were also administered the Mini-International Neuropsychiatric Interview (MINI).

Internal consistency, convergent/criterion validity, item characteristics, and test information were assessed based on the item response theory (IRT), and a factor analysis and cut-off score analyses were conducted. The MHS: A had good internal consistency and good convergent validity with other anxiety scales.

The two versions (online/offline) of the MHS: A were nearly identical (r = 0.908). It had a one-factor structure and showed better diagnostic accuracy (online/offline: sensitivity = 0.98/0.90, specificity = 0.80/0.83) for GAD detection than the GAD-7 and BAI. The IRT analysis indicated that the MHS: A was most informative as a screening tool for GAD.

Conclusions

The MHS: A can serve as a clinically useful screening tool for GAD in Korea. Furthermore, it can be administered both online and offline and can be flexibly used as a brief mental health screener, especially with the current rise in telehealth.

Reference

Kim, S-H., Park, K., Yoon, S., Choi, Y., Lee, S-H. & Choi, K-H. (2021) A Brief Online and Offline (Paper-and-Pencil) Screening Tool for Generalized Anxiety Disorder: The Final Phase in the Development and Validation of the Mental Health Screening Tool for Anxiety Disorders (MHS: A). Frontiers in Psychology. doi: 10.3389/fpsyg.2021.639366. eCollection 2021.

Can We Improve Diagnosis of Depression with XGBOOST Machine Learning Model & a Large Biomarkers Dutch Dataset?

Research Paper Title

Improving Diagnosis of Depression With XGBOOST Machine Learning Model and a Large Biomarkers Dutch Dataset ( n = 11,081).

Abstract

Machine Learning has been on the rise and healthcare is no exception to that. In healthcare, mental health is gaining more and more space. The diagnosis of mental disorders is based upon standardised patient interviews with defined set of questions and scales which is a time consuming and costly process.

The objective of the researchers was to apply the machine learning model and to evaluate to see if there is predictive power of biomarkers data to enhance the diagnosis of depression cases.

In this research paper, they aimed to explore the detection of depression cases among the sample of 11,081 Dutch citizen dataset. Most of the earlier studies have balanced datasets wherein the proportion of healthy cases and unhealthy cases are equal but in their study, the dataset contains only 570 cases of self-reported depression out of 11,081 cases hence it is a class imbalance classification problem. The machine learning model built on imbalance dataset gives predictions biased toward majority class hence the model will always predict the case as no depression case even if it is a case of depression.

The researchers used different resampling strategies to address the class imbalance problem. They created multiple samples by under sampling, over sampling, over-under sampling and ROSE sampling techniques to balance the dataset and then, they applied machine learning algorithm “Extreme Gradient Boosting” (XGBoost) on each sample to classify the mental illness cases from healthy cases.

The balanced accuracy, precision, recall and F1 score obtained from over-sampling and over-under sampling were more than 0.90.

Reference

Sharma, A. & Verbeke, W.J.M.I. (2021) Improving Diagnosis of Depression With XGBOOST Machine Learning Model and a Large Biomarkers Dutch Dataset ( n = 11,081). Frontiers in Big Data. doi: 10.3389/fdata.2020.00015. eCollection 2020.

Linking Boundary Sharpness Coefficient & Cortical Development in Autism Spectrum Disorders

Research Paper Title

Examining the Boundary Sharpness Coefficient as an Index of Cortical Microstructure in Autism Spectrum Disorder.

Background

Autism spectrum disorder (ASD) is associated with atypical brain development. However, the phenotype of regionally specific increased cortical thickness observed in ASD may be driven by several independent biological processes that influence the gray/white matter boundary, such as synaptic pruning, myelination, or atypical migration.

Here, the researchers propose to use the boundary sharpness coefficient (BSC), a proxy for alterations in microstructure at the cortical gray/white matter boundary, to investigate brain differences in individuals with ASD, including factors that may influence ASD-related heterogeneity (age, sex, and intelligence quotient).

Methods

This was a vertex-based meta-analysis and a large multicentre structural magnetic resonance imaging (MRI) dataset, with a total of 1136 individuals, 415 with ASD (112 female; 303 male), and 721 controls (283 female; 438 male).

Results

The researchers observed that individuals with ASD had significantly greater BSC in the bilateral superior temporal gyrus and left inferior frontal gyrus indicating an abrupt transition (high contrast) between white matter and cortical intensities.

Individuals with ASD under 18 had significantly greater BSC in the bilateral superior temporal gyrus and right postcentral gyrus; individuals with ASD over 18 had significantly increased BSC in the bilateral precuneus and superior temporal gyrus.

Increases were observed in different brain regions in males and females, with larger effect sizes in females. BSC correlated with ADOS-2 Calibrated Severity Score in individuals with ASD in the right medial temporal pole. Importantly, there was a significant spatial overlap between maps of the effect of diagnosis on BSC when compared with cortical thickness.

Conclusions

These results invite studies to use BSC as a possible new measure of cortical development in ASD and to further examine the microstructural underpinnings of BSC-related differences and their impact on measures of cortical morphology.

Reference

Olafson, E., Bedford, S.A., Devenyi, G.A., Patel, R., Tullo, S., Park, M.T.M., Parent, O., Anagnostou, E., Baron-Cohen, S., Bullmore, E.T., Chura, L.R., Craig, M.C., Ecker, C., Floris, D.L., Holt, R.J., Lenroot, R., Lerch, J.P., Lombardo, M.V., Murphy, D.G.M., Raznahan, A., Ruigrok, A.N.V., Spncer, M.D., Suckling, Taylor, M.J., MRC AIMS Consortium, Lai, M-C. & Chakravarty, M.M. (2021) Examining the Boundary Sharpness Coefficient as an Index of Cortical Microstructure in Autism Spectrum Disorder. Cerebral Cortex (New York, N.Y.: 1991). doi: 10.1093/cercor/bhab015. Online ahead of print.

Long-Term Depression & Latent Inhibition

Research Paper Title

Disruption of long-term depression potentiates latent inhibition: Key role for central nucleus of the amygdala.

Background

Latent inhibition (LI) reflects an adaptive form of learning, which is impaired in certain forms of mental illness. Glutamate receptor activity is linked to LI, but the potential role of synaptic plasticity remains unspecified.

Methods

Accordingly, the present study examined the possible role of long-term depression (LTD) in LI induced by prior exposure of rats to an auditory stimulus used subsequently as a conditional stimulus (CS) to signal a pending footshock. The researchers employed two mechanistically distinct LTD inhibitors, the Tat-GluA23Y peptide that blocks endocytosis of the GluA2-containing glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), or the selective glutamate n-methyl-d-aspartate receptor (NMDAR) 2B antagonist, Ro25-6981, administered prior to the acquisition of two-way conditioned avoidance with or without tone pre-exposure.

Results

Systemic LTD blockade with the Tat-GluA23Y peptide strengthened the LI effect by further impairing acquisition of conditioned avoidance in CS-pre-exposed rats compared to normal conditioning in non-pre-exposed controls. Systemic Ro25-6981 had no significant effects. Brain-region specific microinjections of the Tat-GluA23Y peptide into the nucleus accumbens, medial prefrontal cortex, central or basolateral amygdala demonstrated that disruption of AMPAR endocytosis in the central amygdala also potentiated the LI effect.

Conclusions

These data revealed a previously unknown role for central amygdala LTD in LI as a key mediator of cognitive flexibility required to respond to previously irrelevant stimuli that acquire significance through reinforcement. The findings may have relevance both for our mechanistic understanding of LI and its alteration in disease states such as schizophrenia, while further elucidating the role of LTD in learning and memory.

Reference

Ashby, D.M., Dias, C., Aleksandrova, L.R., Lapish, C.C., Wang, Y.T. & Phillips, A.G. (2021) Disruption of long-term depression potentiates latent inhibition: Key role for central nucleus of the amygdala. The International Journal of Neuropsychopharmacology. doi: 10.1093/ijnp/pyab011. Online ahead of print.

What is the Role of the Microbiota-Gut-Brain Axis in Mental Health & Medication Response?

Research Paper Title

The Microbiota-Gut-Brain Axis in Mental Health and Medication Response: Parsing Directionality and Causality.

Abstract

There is increasing evidence for the role of the microbiome in various mental health disorders. Moreover, there has been a growing understanding of the importance of the microbiome in mediating both the efficacy and side effects of various medications, including psychotropics.

In this issue, Tomizawa and colleagues report on the effect of psychotropic drugs on the gut microbiome of 40 patients with depression and/or anxiety disorders.

In their longitudinal cohort, the authors find that antipsychotics, but not anxiolytics, decrease microbiome alpha diversity. They further find that antipsychotics dosage was negatively correlated with alpha diversity in these patients.

The health consequences of these microbiome alterations remain to be fully understood. In this commentary, the authors will discuss such findings through the lens of several recent studies on the microbiota-gut-brain axis. They also use the paper as a backdrop to discuss directionality and, by extension, causality in relation to microbiota-gut-brain-brain signalling.

Reference

Bastiaanssen, T.F.S. & Cryan, J.F. (2021) The Microbiota-Gut-Brain Axis in Mental Health and Medication Response: Parsing Directionality and Causality. The International Journal of Neuropsychopharmacology. 24(3), pp.216-220. doi: 10.1093/ijnp/pyaa088.

The Importance of International Patient-Reported Indicators in Mental Health

Research Paper Title

Patient-reported indicators in mental health care: towards international standards among members of the OECD.

Background

Achieving people-centred health care systems requires new and innovative strategies to capture information about whether, and to what degree, health care is successful in improving health from the perspective of the patient. Patient-reported outcome measures (PROMs) and Patient-reported experience measures (PREMs) can bring some of these new insights, and are increasingly used in research, clinical care, and policymaking.

Methods

This paper reflects the ongoing discussions and findings of the OECD PaRIS Working Group on Patient-reported Indicators for Mental Health Care.

Results

The OECD has been measuring quality of care for mental health conditions over the last 14 years through the Health Care Quality and Outcomes (HCQO) programme; nonetheless, information on how persons with mental health problems value the services they receive, and impact of the services, remains limited. As of 2018, a survey from the OECD showed that only five of the twelve countries surveyed (Australia, Israel, Netherlands, Sweden, United Kingdom) reported PROMs and PREMs collection on a regular basis in mental health settings. The paper details some of the challenges specific to the collection and use of PROMs and PREMs in mental health care, and examples from countries which have implemented comprehensive programmes to gather information about PROMs and PREMs for individuals receiving mental health services.

Conclusions

Given the health and economic impact of mental ill-health across all OECD countries, there is significant value to being able to assess the quality and outcomes of care in this area using internationally-comparable measures. Continued international harmonisation of PROMs and PREMs for mental health through international coordination is a key way to facilitate the sharing of national experiences, promote the use of PROMs and PREMs, and create meaningful indicators for national and international benchmarking.

Reference

de Bienassis, K., Kristensen, S., Hewlett, E., Roe, D., Mainz, J. & Klazinga, N. (2021) Patient-reported indicators in mental health care: towards international standards among members of the OECD. International Journal for Quality in Health Care. doi: 10.1093/intqhc/mzab020.