Effect of drama training on self-esteem and personality strengths: A feasibility case control study of nidotherapy.

BACKGROUND: Although there are many case reports and qualitative studies on the likely positive effects of drama on mental health there have been few quantitative studies with mentally ill patients. AIMS: To assess the effect of drama training in patients receiving nidotherapy with a range of mental and personality disorders on changes in self-esteem and personality strengths over a 1-month period compared with two control groups, one with similar mental disorders and another without, who had similar assessments but no acting involvement. METHOD: A total of 19 patients were recruited from a mental health charity with current significant mental illness (active group: n = 6) (b) a control group of patients with current mental illness who were not involved in acting (n = 5), and an additional control group with no current mental illness (n = 8) The patients involved in drama were taking part in nidotherapy, an environmental intervention. Two self-rating scales, the Rosenberg Self-Esteem Scale (RSES) and Abbreviated Personality Strengths Scale (APSS) recorded changes in self-esteem and personality strengths at base-line and after 1 month in the participants. Random effects modelling was used to analyse the data. RESULTS: The intervention group showed positive improvement in personality strengths (p = .009) compared to the control group that had no mental illness, and also improved more than the control group with mental illness but not to a significant degree (p = .16). Self-esteem recorded with the Rosenberg scale was lower in those in the acting group at baseline compared with the other two groups (p = .088) but after acting training improved by 29% to be equivalent to the control groups. CONCLUSIONS: Despite the limited numbers in this study, and the consequent inability to make firm conclusions about the efficacy of drama therapy as part of nidotherapy, the findings suggest that larger trials of this approach are feasible and worth exploring. .

ADCT-602, a Novel PBD Dimer-containing Antibody-Drug Conjugate for Treating CD22-positive Hematologic Malignancies.

Relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) and lymphomas have poor patient outcomes; novel therapies are needed. CD22 is an attractive target for antibody-drug conjugates (ADCs), being highly expressed in R/R B-ALL with rapid internalization kinetics. ADCT-602 is a novel CD22-targeting ADC, consisting of humanized mAb hLL2-C220, site specifically conjugated to the pyrrolobenzodiazepine dimer-based payload tesirine. In preclinical studies, ADCT-602 demonstrated potent, specific cytotoxicity in CD22-positive lymphomas and leukemias. ADCT-602 was specifically bound, internalized, and trafficked to lysosomes in CD22-positive tumor cells; after cytotoxin release, DNA interstrand crosslink formation persisted for 48 hours. In the presence of CD22-positive tumor cells, ADCT-602 caused bystander killing of CD22-negative tumor cells. A single ADCT-602 dose led to potent, dose-dependent, in vivo antitumor activity in subcutaneous and disseminated human lymphoma/leukemia models. Pharmacokinetic analyses (rat and cynomolgus monkey) showed excellent stability and tolerability of ADCT-602. Cynomolgus monkey B cells were efficiently depleted from circulation after one dose. Gene signature association analysis revealed IRAK1 as a potential marker for ADCT-602 resistance. Combining ADCT-602 + pacritinib was beneficial in ADCT-602-resistant cells. Chidamide increased CD22 expression on B-cell tumor surfaces, increasing ADCT-602 activity. These data support clinical testing of ADCT-602 in R/R B-ALL (NCT03698552) and CD22-positive hematologic cancers.

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.

DSM-5 conduct disorder and symptoms in youths at high risk of psychosis in Kenya with DSM-5 mental disorders and substance use: towards integrated management.

Little is known about the prevalence of Conduct Disorder (CD) and symptoms of CD in high risk psychosis persons at both clinical and community populations in LMICs and in particular Kenya. This study aimed to document (1) the prevalence of CD diagnosis and symptoms in youth who screened positive for psychosis and (2) the associated mental disorders and substance use in the same cohort in LMIC. The sample size was 536 students who had screened positive on the Washington Early Recognition Center Affectivity and Psychosis (WERCAP) from a population of 9,742 high school, college and university students, but had not converted to a psychotic disorder. We collected data on socio-demographic characteristics and used the following tools: Economic indicators tool; the Diagnostic Interview Schedule (DIS) tool for DSM-5 diagnosis; World Health Organization (WHO) Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). Basic descriptive statistics, chi-square test, Fisher's exact test, Pearson correlation and Poisson regression were conducted. Five percent (5%) of the respondents met the criteria for DSM-5 CD. Indeterminate CD comprised 10.1%. Male gender, all substances except hallucinogens lifetime, obsessive compulsive disorder, psychosis, agoraphobia, social phobia, drug abuse/dependence, antisocial personality disorder, oppositional defiant disorder, suicidality, WERCAP screen for bipolar disorder and WERCAP screen for schizophrenia were significantly (p < 0.05) associated with CD. Deceitfulness or theft criteria symptoms showed that CD had no significant gender difference. Criteria symptoms in aggression to people and animals, destruction of property and serious violations of rules were more common among males. Our findings suggest the need to screen for and diagnose CD, mental disorders and substance use in high risk psychosis youths in Kenya. This will inform integrated management.

The effect of environmental change, planned and unplanned life events on the long-term outcome of common mental disorders.

PURPOSE: To examine the nature of positive and negative environmental change on clinical outcome in 210 patients presenting with anxiety and depression and followed up over 30 years. METHODS: In addition to clinical assessments, major environmental changes, particularly after 12 and 30 years, were recorded in all patients by a combination of self-report and taped interviews. Environmental changes were separated into two major groups, positive or negative, determined by patient opinion. RESULTS: In all analyses positive changes were found to be associated with better outcome at 12 years with respect to accommodation (P = 0.009), relationships (P = 007), and substance misuse (P = 0.003), with fewer psychiatric admissions (P = 0.011) and fewer social work contacts at 30 years (P = 0.043). Using a consolidated outcome measure positive changes were more likely than negative ones to be associated with a good outcome at 12 and 30 years (39% v 3.6% and 30.2% v 9.1%, respectively). Those with personality disorder at baseline had fewer positive changes (P = 0.018) than others at 12 years and fewer positive occupational changes at 30 years (P = 0.041). Service use was greatly reduced in those with positive events with 50-80% more time free of all psychotropic drug treatment (P < 0.001). Instrumental positive change had greater effects than imposed changes. CONCLUSIONS: Positive environmental change has a favourable impact on clinical outcome in common mental disorders. Although studied naturalistically in this study the findings suggest that if harnessed as a therapeutic intervention, as in nidotherapy and social prescribing, it would yield therapeutic dividends.

Madness and society in Britain.

The fiftieth anniversary of the Royal College of Psychiatrists, and the publication of a detailed multidisciplinary social history of British psychiatry and mental health in recent decades have offered an opportunity to take a helicopter view and reflect on the relation between psychiatry and changing British society. We argue that the time has come to move on from the rhetoric of deinstitutionalisation and community mental healthcare to lead public debate and advocacy for the needs of the mentally ill in the new era of 'meta-community psychiatry and mental healthcare'. We need to respond effectively to the increasing awareness of mental health problems across society, aiming for a pluralist, integrated and well-funded reform led by joint professional and patient interests which could be unstoppable if we all work together.

Response: Personality disorder is here to stay across the lifespan - a response to Commentaries on the May 2022 Debate.

BACKGROUND: The classification of personality disorder is in a state of flux. Revision is necessary, overdue, and is provided by the new ICD-11 classification. AIMS: To explain the advantages of the new classification system and why 'borderlne' is a redundant term. To summarise positive and negative views about its implications, especially in young people. MATERIALS AND METHODS: Review of recent literature and developments. RESULTS: Personality disturbance is ubiquitous and changes across the life span. The data are unequivocal. DISCUSSION: As personality disturbance is so common in childhood and adolescence it should be recognised and acknowledged at this time even though it is very likely to change. CONCLUSIONS: The stigma surrounding personality disorder can be countered by science and courage.

The recording of personality strengths: An analysis of the impact of positive personality features on the long-term outcome of common mental disorders.

Although personality strengths are assessed frequently in occupational and managerial settings and in children, they have been less used in studies of personality disorder. The aim of this study is to examine the impact of a measure of personality strengths derived from the comprehensive version of the Personality Assessment Schedule (CPAS) (i.e., positive and reinforcing traits) on clinical symptoms and functioning. Eighty-nine patients with anxiety and depression seen at the 30-year follow-up point in a cohort study (Nottingham Study of Neurotic Disorder) were administered the Comprehensive version of the PAS (CPAS). A factor analysis of the results determined the main groupings and their impact on long-term outcomes as well as their association with change of outcomes over 30 years. Five positive factors (strengths), forceful considerateness, emotional toughness, cautiousness, independence and discernment accounted for 67.2% of the variance using both Varimax and Promax rotations. Low positive scores were strongly associated with suicide attempts, moderate/severe personality disorder, cothymia (mixed anxiety-depression), greater symptomatology and poor social function. High scores were protective of serious pathology and particularly effective in inhibiting suicidal behaviour. The promotion of personality strengths may be of value in preventing suicidal behaviour and helping pro-social change in those with personality disturbance.

Mindfulness-based intervention in patients with persistent pain in chest (MIPIC) of non-cardiac cause: a feasibility randomised control study.

OBJECTIVE: The study evaluated the feasibility of mindfulness-based cognitive therapy (MBCT) in patients with non-cardiac chest pain by assessing their willingness to participate and adhere to the programme, and for these data to help further refine the content of MBCT for chest pain. PATIENTS AND METHODS: This prospective 2:1 randomised controlled trial compared the intervention of adapted MBCT as an addition to usual care with just usual care in controls. Among 573 patients who attended the rapid access chest pain clinic over the previous 12 months and were not diagnosed with a cardiac cause but had persistent chest pain were invited. The intervention was a 2-hour, weekly, online guided 8-week MBCT course. Compliance with attendance and the home practice was recorded. Enrolled patients completed the Seattle angina questionnaire (SAQ), Hospital Anxiety and Depression Scale, Cardiac Anxiety Questionnaire, Five-Facet Mindfulness Questionnaire, and Euro Quality of Life-5 Dimensions-5 Level at baseline assessment and after 8-week period. RESULTS: Persistent chest pain was reported by 114 patients. Of these, 33 (29%) patients with a mean age of 54.2 (±12.2) years and 68% women, consented to the study. Baseline questionnaires revealed mild physical limitation (mean SAQ, 76.8±25), high levels of anxiety (76%) and depression (53%), modest cardiac anxiety (CAQ,1.78±0.61) and mindfulness score (FFMQ, 45.5±7.3). Six patients subsequently withdrew due to bereavement, caring responsibilities and ill health. Of the remaining 27 participants, 18 in the intervention arm attended an average of 5 sessions with 61% attending ≥6 sessions. Although not statistically powered, the study revealed a significant reduction in general anxiety, improved mindfulness and a trend towards improvement in SAQ scores in the intervention arm. CONCLUSION: One-third of patients with persistent non-cardiac chest pain were willing to participate in mindfulness-based therapy. An improvement in anxiety and mindfulness was detected in this feasibility study. A larger trial is required to demonstrate improvement in chest pain symptoms.

Matching ICD-11 personality status to clinical management in a community team-The Boston (UK) Personality Project: Study protocol.

Epidemiological studies show 30% to 50% of all patients in community mental health teams have personality disorders. These are normally comorbid with other psychiatric disorders, often as Galenic syndromes, and are seldom identified. In the Boston (UK) Personality Project all patients under a community health service in Boston in Lincolnshire will be asked to agree to have their personality status assessed using scales recording the new ICD-11 classification, together with clinical ratings, social function and satisfaction. A control group of 100 patients from an adjacent service of similar demographics (Spalding) will also have similar ratings but no personality assessments. Changes in clinical status, social function and service satisfaction will be made after 6 and 12 months in both groups. The patients in the Boston group will be offered matched interventions using a stepped care approach for both the severity of disorder and its domain structure. These interventions will include shorter versions of existing psychological treatments, environmental therapies including nidotherapy, adaptive and acceptance models, drug reduction and social prescribing. Full costs of psychiatric care will be measured in both groups. The main hypothesis is that greater awareness of personality function will lead to better clinical outcomes and satisfaction.

The influence of personality disorder in predicting suicidal behaviour in common mental disorders: A 30-year study.

Two hundred ten patients with anxiety and depressive disorders were followed up over 30 years. Personality status was assessed at baseline using the Personality Assessment Schedule (PAS), an instrument that classifies personality disorder in a similar way to the new ICD-11 classification. Assessments of suicidal behaviour were made at 5, 12 and 30 years and suicidal thoughts at 12 and 30 years and analysed by personality status, clinical diagnosis and scores on the General Neurotic Syndrome Scale, a combined diagnosis of mixed anxiety depression and personality dysfunction. Suicide attempts were most frequent in the first 5 years of the study and reduced over time. Baseline personality status was the best predictor of suicide attempts at 5 years (no personality disorder 29.3%, personality disorder 51.6%, p = 0.006), and at 12 years (no personality disorder 11.9%, personality disorder 25.7%, p = 0.042), but no important differences were found at 30 years, when comorbid mental state disorder was the strongest predictor (p < 0.001). Similar but less marked findings were found for the general neurotic syndrome. It is concluded that the presence of personality disorder is a robust predictor of suicidal behaviour in the shorter term but in the long-term comorbid pathology is a better predictor.

Debate: Young people with personality disorder should be recognised and appropriately managed.

The characteristic features of personality disorder that are found in older people are also present in young people. These features are currently not diagnosed as personality problems by most UK practitioners, through a mixture of fear and prejudice, which is used to justify this avoidant diagnostic behaviour. A simple solution is offered. State that personality function is 'disordered' in those who cross the threshold for diagnosis but emphasise that it is often ephemeral and can be managed.

Relationships between treatments received in the Nottingham Study of Neurotic Disorder over 30 years and personality status.

We compared the drug treatments and health service contacts of anxious and depressed patients separated by personality disturbance in 200 patients over 30 years. Contact details with health professionals at 5, 12 and 30 years were recorded and analysed by multilevel models at all time points. Over 30 years, patients with dependent and anankastic personality disturbance and cothymia (the general neurotic syndrome) were 2.27 times more likely to receive selective serotonin reuptake inhibitors (SSRIs) and new antidepressants (95% confidence interval [CI]: 1.22-4.24), particularly paroxetine, and were 1.6 weeks (95% CI: 1.2-2.3) longer on the drug than those without the syndrome. Similar results with SSRIs and new antidepressants in patients with personality disorder fell short of significance after adjusting for age, sex and DSM status. Most patients had a DSM diagnosis at follow-up points, and these had increased psychological treatment, psychiatric admissions, multiple drugs, SSRIs and new antidepressants. At later follow-up, most drug treatments decreased apart from psychological treatment, SSRIs and new antidepressants, and baseline personality disorder had little impact on treatment histories compared with others. We conclude that the (Galenic) general neurotic syndrome is associated with greater use of treatments in the long term, showing that combined personality and symptomatic pathology overcomes that of personality disorder alone.

Galenic syndromes: combinations of mental state and personality disorders too closely entwined to be separated.

Many mental disorders are linked to personality, but this is rarely recognised in clinical practice. It is suggested here that when the links are very close, the two can be joined. Galenic syndromes are so named because Galen was the first physician to recognise the links between personality and disease.

Preclinical Development of ADCT-601, a Novel Pyrrolobenzodiazepine Dimer-based Antibody-drug Conjugate Targeting AXL-expressing Cancers.

AXL, a tyrosine kinase receptor that is overexpressed in many solid and hematologic malignancies, facilitates cancer progression and is associated with poor clinical outcomes. Importantly, drug-induced expression of AXL results in resistance to conventional chemotherapy and targeted therapies. Together with its presence on multiple cell types in the tumor immune microenvironment, these features make it an attractive therapeutic target for AXL-expressing malignancies. ADCT-601 (mipasetamab uzoptirine) is an AXL-targeted antibody-drug conjugate (ADC) comprising a humanized anti-AXL antibody site specifically conjugated using GlycoConnect technology to PL1601, which contains HydraSpace, a Val-Ala cleavable linker and the potent pyrrolobenzodiazepine (PBD) dimer cytotoxin SG3199. This study aimed to validate the ADCT-601 mode of action and evaluate its efficacy in vitro and in vivo, as well as its tolerability and pharmacokinetics. ADCT-601 bound to both soluble and membranous AXL, and was rapidly internalized by AXL-expressing tumor cells, allowing release of PBD dimer, DNA interstrand cross-linking, and subsequent cell killing. In vivo, ADCT-601 had potent and durable antitumor activity in a wide variety of human cancer xenograft mouse models, including patient-derived xenograft models with heterogeneous AXL expression where ADCT-601 antitumor activity was markedly superior to an auristatin-based comparator ADC. Notably, ADCT-601 had antitumor activity in a monomethyl auristatin E-resistant lung-cancer model and synergized with the PARP inhibitor olaparib in a BRCA1-mutated ovarian cancer model. ADCT-601 was well tolerated at doses of up to 6 mg/kg and showed excellent stability in vivo. These preclinical results warrant further evaluation of ADCT-601 in the clinic.

Specialist teams as constituted are unsatisfactory for treating people with personality disorders.

It is now becoming standard practice in most advanced economies to provide specialist services for those with personality disorder. Such services, almost exclusively, provide complex well-structured psychological interventions lasting many months for a small number of those with borderline personality disorder pathology. The evidence suggests that these treatments are effective but they can only be provided for a small number of people. However, in every area the numbers of patients with significant personality disorder far exceeds those that are treated, and most of these have other personality disorders. It is argued that the current service system is not working efficiently and should be replaced by one that provides resources and expertise within community teams with some external advice from specialists but no transfer of responsibility to a designated team.