Pharmacological management of fragile X syndrome: a systematic review and narrative summary of the current evidence.

INTRODUCTION: Fragile X syndrome (FXS) is the most common inherited cause of Intellectual Disability. There is a broad phenotype that includes deficits in cognition and behavioral changes, alongside physical characteristics. Phenotype depends upon the level of mutation in the FMR1 (fragile X messenger ribonucleoprotein 1) gene. The molecular understanding of the impact of the FMR1 gene mutation provides an opportunity to target treatment not only at symptoms but also on a molecular level. METHODS: We conducted a systematic review to provide an up-to-date narrative summary of the current evidence for pharmacological treatment in FXS. The review was restricted to randomized, blinded, placebo-controlled trials. RESULTS: The outcomes from these studies are discussed and the level of evidence assessed against validated criteria. The initial search identified 2377 articles, of which 16 were included in the final analysis. CONCLUSION: Based on this review to date there is limited data to support any specific pharmacological treatments, although the data for cannabinoids are encouraging in those with FXS and in future developments in gene therapy may provide the answer to the search for precision medicine. Treatment must be person-centered and consider the combination of medical, genetic, cognitive, and emotional challenges.

A pragmatic randomized controlled exploratory trial of the effectiveness of Eye Movement Desensitization and Reprocessing therapy for psychotic disorder.

BACKGROUND: People with severe mental illness are often excluded from trials related to Eye Movement Desensitization and Reprocessing (EMDR) therapy. Principal concerns are that they may not tolerate treatment, might risk relapse or that psychotic symptoms may worsen. There is however building evidence of a traumatogenic etiology of psychotic disorder that may benefit therapeutically from EMDR. However, EMDR in this role is done mainly in specialist tertiary settings. AIM: To conduct a randomized exploratory trial of prospective treatment of EMDR for people with psychotic disorder and a history of trauma in an adult community mental health service. METHODS: A randomized exploratory trial with a controlled pilot design was employed to conduct a prospective treatment and six-month follow-up study with an interim 10-week analysis in a rural county in the UK (population 538,000). We recruited participants with psychotic disorder who had a reported history of trauma and were interested in receiving trauma therapy. They were then randomized to either receive EMDR or treatment as usual (TAU). The primary instrument used was the Impact of Events Scale (IES) with secondary instruments of Positive and Negative Symptoms of Psychotic Disorder (PANSS), PTSD Checklist (PCL-C), and subjective Quality of Life (MANSA). RESULTS: IES scores showed significant improvements in the EMDR group (n = 24, age 42.0 SD (14.5), 42% male) compared to the TAU group (n = 12, age 34.4 SD (11.3), 50% male) at 10 weeks and at six months (p < 0.05). There were significant improvements in PCL-C and PANSS negative symptoms scores associated with treatment (p < 0.05). All other scales showed positive trends. CONCLUSIONS: This study demonstrates that EMDR can reduce the impact of traumatic events for patients with a psychotic disorder in a clinical setting in the UK. The improvements in psychotic disorder persisted for six months after treatment. TRIAL REGISTRATION: ISRCTN43816889.

The views of psychiatrists on proposed changes to the England and Wales Mental Health Act 1983 legislation for people with intellectual disability: A national study.

BACKGROUND: The Draft Mental Health Bill proposes removal of both intellectual disability and autism from Section 3 of the Mental Health Act for England and Wales (MHA). This would lead to people with intellectual disability (PwID) and/or autism could not be detained beyond 28 days, in the absence of diagnosed co-occurring mental illness. AIM: To obtain views of psychiatrists working with PwID in England and Wales regarding the proposed MHA changes. This study focusses specifically on the impact on PwID. METHODS: A cross-sectional online mixed methodology survey of Likert and free-text response questions was developed, to ascertain perceptions of proposed legislative changes to the MHA. A non-discriminatory exponential snowballing technique leading to non-probability sampling was used to disseminate the survey. Quantitative data was analysed using descriptive statistics, Mann-Whitney and Fisher's exact tests. Thematic analysis was conducted on free text responses. RESULTS: A total of 82 psychiatrists (33%) from approximately 250 eligible completed the survey. Nearly two-thirds (64%) reported good awareness of the proposed changes, with over half (55%) reporting disagreement with the changes. Psychiatrists working in inpatient settings for PwID reported increased awareness of the changes, less agreement with the reforms, and increased expectations of the reforms having negative unintended consequences, compared to their peers working exclusively in the community. Consultants reported greater disagreement with the changes compared to their non-consultant peers. Qualitative analysis identified five main themes: impact on diagnosis and treatment, seeking alternative options, introducing inequities, resources, and meeting holistic care goals through the Care, Education and Treatment Reviews (CETR) process. CONCLUSION: Psychiatrists working with PwID report widespread disagreement with the proposed changes to the MHA for PwID, with greater levels of disagreement among those working in inpatient services. Caution with respect to the proposed changes, and monitoring of the impact of the changes if implemented, is advised.

Mortality risk in adults with intellectual disabilities and epilepsy: an England and Wales case-control study.

BACKGROUND: People with epilepsy (PWE) and people with intellectual disabilities (ID) both live shorter lives than the general population and both conditions increase the risk of death further. We aimed to measure associations between certain risk factors for death in PWE and ID. METHODS: A retrospective case-control study was conducted in ten regions in England and Wales. Data were collected on PWE registered with secondary care ID and neurology services between 2017 and 2021. Prevalence rates of neurodevelopmental, psychiatric and medical diagnoses, seizure frequency, psychotropic and antiseizure medications (ASM) prescribed, and health activity (epilepsy reviews/risk assessments/care plans/compliance etc.) recorded were compared between the two groups. RESULTS: 190 PWE and ID who died were compared with 910 living controls. People who died were less likely to have had an epilepsy risk assessment but had a greater prevalence of genetic conditions, older age, poor physical health, generalized tonic-clonic seizures, polypharmacy (not ASMs) and antipsychotic use. The multivariable logistic regression for risk of epilepsy-related death identified that age over 50, medical condition prevalence, antipsychotic medication use and the lack of an epilepsy review in the last 12 months as associated with increased risk of death. Reviews by psychiatrists in ID services was associated with a 72% reduction in the odds of death compared neurology services. CONCLUSIONS: Polypharmacy and use of antipsychotics may be associated with death but not ASMs. Greater and closer monitoring by creating capable health communities may reduce the risk of death. ID services maybe more likely to provide this holistic approach.

Who cares? A scoping review on intellectual disability, epilepsy and social care.

PURPOSE: Nearly a quarter of people with Intellectual disability (PwID) have epilepsy. Many have seizures across their lifetime. In the UK supporting their epilepsy linked risks and needs, particularly in professional care settings and in the community, requires significant social care input. Therefore, the interface between social and health care services is important. This study aim is to identify key intersectional areas of social provision for PWID and epilepsy. METHODS: A scoping review of the literature was performed in accordance with PRISMA guidance with suitable search terms. The search was completed in CINAHL, Embase, Psych INFO, SCIE, and Cochrane electronic databases by an information specialist. A quality assessment was completed for the included studies where appropriate. The included studies were analysed qualitatively to identify key themes and provide a narrative description of the evidence by two reviewers. RESULTS: Of 748 papers screened, 94 were retrieved. Thirteen articles met the inclusion criteria with a range of methodologies. A thematic analysis generated four key categories for significant social care involvement i.e., staff training and education; emergency seizure management; holistic approach to care; and nocturnal monitoring and supervision. CONCLUSIONS: PwID with epilepsy have support needs that require fulfilling by various aspects of special care provision, many within the social ambit. Inspite of evidence of these needs and recurrent calls to work jointly with social care providers this has not happened. There is limited research into social care role in epilepsy management in PwID which needs addressing.

The role of mindfulness training in sustaining weight reduction: retrospective cohort analysis.

BACKGROUND: Psychological stress has an established bi-directional relationship with obesity. Mindfulness techniques reduce stress and improve eating behaviours, but their long-term impact remains untested. CALMPOD (Compassionate Approach to Living Mindfully for Prevention of Disease) is a psychoeducational mindfulness-based course evidenced to improve eating patterns across a 6-month period, possibly by reducing stress. However, no long-term evaluation of impact exists. AIMS: This study retrospectively evaluates 2-year outcomes of CALMPOD on patient engagement, weight and metabolic markers. METHOD: All adults with a body mass index >35 kg/m2 attending an UK obesity service during 2016-2020 were offered CALMPOD. Those who refused CALMPOD were offered standard lifestyle advice. Routine clinic data over 2 years, including age, gender, 6-monthly appointment attendance, weight, haemoglobin A1C and total cholesterol, were pooled and analysed to evaluate CALMPOD. RESULTS: Of 289 patients, 163 participated in the CALMPOD course and 126 did not. No baseline demographic differences existed between the participating and non-participating groups. The CALMPOD group had improved attendance across all 6-monthly appointments compared with the non-CALMPOD group (P < 0.05). Mean body weight reduction at 2 years was 5.6 kg (s.d. 11.2, P < 0.001) for the CALMPOD group compared with 3.9 kg (s.d. 10.5, P < 0.001) for the non-CALMPOD group. No differences in haemoglobin A1C and fasting serum total cholesterol were identified between the groups. CONCLUSIONS: The retrospective evaluation of CALMPOD suggests potential for mindfulness and compassion-based group educational techniques to improve longer-term patient and clinical outcomes. Prospective large-scale studies are needed to evaluate the impact of stress on obesity and the true impact of CALMPOD.

International clinician perspectives on pandemic-associated stress in supporting people with intellectual and developmental disabilities.

BACKGROUND: People living with intellectual and developmental disabilities (IDD) have suffered disproportionately in health outcomes and general well-being during the COVID-19 pandemic. There is emerging evidence of increased psychological distress. Increased strain has also fallen on clinicians managing the psychological needs of people with IDD, in the context of learning new technologies, staff shortages, reduced services and paused training opportunities. AIMS: To examine clinicians' experiences of patient care, clinical management and the impact of care delivery. METHOD: A mixed fixed-response and free-text survey comprising 28 questions covering four areas (responder demographics, clinical practice, changes to local services and clinician experiences) was developed, using the STROBE guidance. It was disseminated through an exponential snowballing technique to clinicians in seven high-income countries. Quantitative data were analysed and presented with Microsoft Excel. Qualitative data were coded and thematically analysed, and presented with in-text quotations. RESULTS: There were 139 respondents, mostly senior physicians (71%). Two-thirds reported over 10 years working in the field. Quantitative findings include increased clinician stress (77%), referrals (53%), patient distress presentations (>70%), patient isolation (73%) and carer burden (89%), and reduced patient participation in daily activities (86%). A third reported increased psychotropic prescribing. Qualitative analysis outlined changes to clinical practice, particularly the emergence and impact of telehealth. CONCLUSIONS: In the countries surveyed, the pandemic has not only had a significant impact on people with IDD, but also their carers and clinicians. A proactive, holistic international response is needed in preparedness for future public health emergencies.

EEG Markers in Emotionally Unstable Personality Disorder-A Possible Outcome Measure for Neurofeedback: A Narrative Review.

Objectives. There is growing evidence for the use of biofeedback (BF) in affective disorders, dissocial personality disorder, and in children with histories of abuse. Electroencephalogram (EEG) markers could be used as neurofeedback in emotionally unstable personality disorder (EUPD) management especially for those at high risk of suicide when emotionally aroused. This narrative review investigates the evidence for EEG markers in EUPD. Methods. PRISMA guidelines were used to conduct a narrative review. A structured search method was developed and implemented in collaboration with an information specialist. Studies were identified via 3 electronic database searches of MEDLINE, Embase, and PsycINFO. A predesigned inclusion/exclusion criterion was applied to selected papers. A thematic analysis approach with 5 criteria was used. Results. From an initial long list of 5250 papers, 229 studies were identified and screened, of which 44 met at least 3 of the predesigned inclusion criteria. No research to date investigates EEG-based neurofeedback in EUPD. A number of different EEG biomarkers are identified but there is poor consistency between studies. Conclusions. The findings heterogeneity may be due to the disorder complexity and the variable EEG related parameters studied. An alternative explanation may be that there are a number of different neuromarkers, which could be clustered together with clinical symptomatology, to give new subdomains. Quantitative EEGs in particular may be helpful to identify more specific abnormalities. EEG standardization of neurofeedback protocols based on specific EEG abnormalities detected may facilitate targeted use of neurofeedback as an intervention in EUPD.

Quality improvement in the management of people with epilepsy and intellectual disability: the development of clinical guidance.

Introduction: This clinical guidance looks at the specific concerns of delivery of medical treatment for people with epilepsy and intellectual disability (ID). People with ID have not been included in licensing drug trials of AEDs. However, this population has an over-representation of seizure comorbidity, treatment resistance, and polypharmacy while also being vulnerable to not having their views considered.Areas covered: This review summarizes the current most robust evidence available for the use of licensed AEDs in people with epilepsy and ID. The article provides practical evidence-based clinical information to help prescribers choose the most appropriate AED from the drugs discussed. The article highlights other important individualized factors to consider before initiating or changing antiepileptic medication.Expert opinion: A 'traffic light' coding system is applied to commonly used AEDs based on the level of evidence and expert clinical experience. Managing epilepsy in the ID population requires specialist care. Treatment plans need to be holistic and tailored to accommodate an individual's comorbidities, concurrent medications, general health, social and environmental status. There is a need for large quality trial data to assess the most suitable AEDs on seizure control and quality of life in this population with complex needs.

Abnormal cortical asymmetry as a target for neuromodulation in neuropsychiatric disorders: A narrative review and concept proposal.

Recent advances in knowledge relating to the organization of neural circuitry in the human brain have increased understanding of disorders involving brain circuit asymmetry. These asymmetries, which can be measured and identified utilizing EEG and LORETA analysis techniques, may be a factor in mental disorders. New treatments involving non-invasive brain stimulation (NIBS), including trans-cranial magnetic stimulation, direct current stimulation and vagal nerve stimulation, have emerged in recent years. We propose that EEG identification of circuit asymmetry geometries can direct non-invasive brain stimulation more specifically for treatments of mental disorders. We describe as a narrative review new NIBS therapies that have been developed and delivered, and suggest that they are proving effective in certain patient groups. A brief narrative of influence of classical and operant conditioning of neurofeedback on EEG coherence, phase, abnormalities and Loreta's significance is provided. We also discuss the role of Heart rate variability and biofeedback in influencing EEG co-relates. Clinical evidence is at an early stage, but the basic science evidence and early case studies suggest that this may be a promising new modality for treating mental disorders and merits further research.

Momordica charantia seed extract exhibits strong anticoagulant effect by specifically interfering in intrinsic pathway of blood coagulation and dissolves fibrin clot.

The current study explores the anticoagulant and fibrin clot-hydrolyzing properties of Momordica charantia seed extract (MCSE). MCSE hydrolyzed casein with the specific activity of 0.780 units/mg per min. Interestingly, it enhanced the clot formation process of citrated human plasma from control 146 to 432 s. In addition, the intravenous injection of MCSE significantly prolonged the bleeding time in a dose-dependent manner from control 150 to more than 800 s, and strengthened its anticoagulant activity. Interestingly, MCSE specifically prolonged the clotting time of only activated partial thromboplastin time, but not prothrombin time, and revealed the participation of MCSE in the intrinsic pathway of the blood coagulation cascade. Furthermore, MCSE completely hydrolyzed both Aα and Bß chains of the human fibrinogen and partially hydrolyzed the γ chain. However, it hydrolyzed all the chains (α polymer, α chain, ß chain and γ-γ dimmers) of partially cross-linked human fibrin clot. The proteolytic activity followed by the anticoagulant effect of the MCSE was completely abolished by the 1,10-phenanthroline and phenyl methyl sulphonyl fluoride, but iodoacetic acid, EDTA, and ethylene glycol-N,N,N',N'-tetra acetic acid did not. Curiously, MCSE did not hydrolyze any other plasma proteins except the plasma fibrinogen. Moreover, MCSE was devoid of RBC lysis, edema and hemorrhagic properties, suggesting its nontoxic nature. Taken together, MCSE may be a valuable candidate in the treatment of blood clot/thrombotic disorders.