bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Case for Cerebellar Neuromodulation in Affective Disorders
Authors: O'Neill-Kerr Alex , Bandara Harshani Yapa , Hristova Nadia 
Published: August 2024

AimsThis case report focuses on a 68-year-old Caucasian female, with long-standing symptoms of executive and cerebellar dysfunction, which responded well to rTMS targeting the prefrontal cortex and cerebellum.MethodsThis patient was seen in the private sector for long-standing symptoms of low mood, mental fog, unsteady gait, along with slurred speech and poor vision. History indicated the possibility of multiple mini strokes several years earlier, which may have contributed to her current presentation, and MRI Brain confirmed diffuse small vessel disease in periventricular areas and deep white matter, with no atrophy of brainstem or cerebellum. Her medications at the time included venlafaxine 75 mg OD, atorvastatin 20 mg OD, amlodipine 5 mg OD, thiamine HCL 100 mg OD and aspirin 75 mg. She then had a course of standard rTMS (F3 and F4), to which she had no real response. The team then performed a Quantitative Electroencephalography which revealed bilateral prefrontal and cerebellar disconnection, with normal connectivity in the rest of the brain and cortex, which enabled a diagnosis of Organic mood (affective) disorder, F06.3.Based on the above findings, she was then prescribed a course of rTMS as follows:
1.Bifrontal excitatory Theta burst, at 50–60%, daily for 20 treatments.2.CB1 and CB2 Cerebellar iTBS (10min) at 50–60%, daily for 20 treatments.Mid treatment review showed improvement in depression and anxiety, mirrored by significant reductions in psychometric scores compared to baseline, although her memory, concentration and motivation remained poor, and it was agreed that she would be reviewed again after completion of 20 sessions.ResultsAlthough long known for its function in fine tuning motor function, emerging research indicates the growing importance of the cerebellum and its neural connections in neuropsychiatric disorders.Recent studies have shown that those with cerebellar damage show impairments in executive function, and emotional regulation, in addition to language deficits and problems with sensory processing. It is bidirectionally connected with areas associated with processing social salience, including the posterior parietal and prefrontal cortex. With its connections to the prefrontal cortex, limbic structures and monoamine producing brainstem areas, it is likely the cerebellum also plays a key role in fine tuning emotional output, which appears to be corroborated by functional neuroimaging.ConclusionThis case further supports the emerging evidence base that the cerebellum plays a key role in emotional experience, along with the prospect of using targeted rTMS for therapeutic benefit.
Challenges in Investigating Psychotic-Like Experiences in an Adolescent Awaiting an Autism Assessment
Authors: Parkinson Jade 
Published: August 2024

AimsStudies estimate that 90% of people with a diagnosis of autism experience sensory abnormalities. The majority of those affected will not have a psychotic illness, however young people with autism are three to six times more likely to develop schizophrenia than their neurotypical equivalents.This report considers the diagnostic complexities, potential risks and challenges of navigating concurrent referral and treatment pathways for an adolescent awaiting an autism assessment, who has psychotic-like experiences.MethodsAn adolescent female was referred to our Tier 3 service for an autism assessment. Whilst on the waiting list, our service was contacted on three occasions by adults who knew the patient, expressing concerns that she had psychotic-like experiences, namely perceptual abnormalities which had not been included in the original referral.On the third occasion, approximately six months after the initial referral was accepted, a decision was made to review the patient face-to-face to explore these symptoms further.During this review she appeared to have positive and negative symptoms of schizophrenia, including perceptual abnormalities in all sensory modalities, thought block, paranoid ideation and a mood incongruent affect. Her sleep cycle was reversed and she had not attended school for several years.She was subsequently referred to the Early Intervention Psychosis Service, underwent an eight week assessment and was discharged back to the autism service.ResultsYoung people in the UK are on average waiting nine months for an autism assessment, although some are waiting up to seven years for treatment. NICE recommends that young people referred due to first episodes of psychosis are seen within two weeks, as delays in treatment can negatively impact on the patient's response to treatment.Diagnostic uncertainty can arise due to overlapping symptoms, clinician inexperience and difficulties with eliciting a thorough history. With waiting times for autism assessments growing, young people who may have psychotic symptoms are waiting longer to see a clinician. The referral pathways for neurodevelopmental and psychiatric disorders typically exist independently, but inclusion on one pathway can create barriers in accessing the other.ConclusionIt is good practice for comorbid psychiatric disorders to be considered by the referrer, when referring a young person for an autism assessment.Clinicians should avoid making assumptions regarding the aetiology of symptoms based on the original reason for referral, explore symptoms thoroughly and refer to alternative services if needed.
Trajectories of Psychotropic Medications Before and After an Autism Diagnosis Vary by Age and Sex
Authors: Brodeur Sébastien , Dufour Isabelle , Chiu Yohann , Courteau Josiane , Couture Mélanie 
Published: August 2024

AimsInterventions to support people with autism are multidimensional, but primarily psychosocial in nature. These interventions include behavioural, educational and support therapies. Some psychotropic medications are used to manage medical and psychiatric comorbidities associated with autism, which interfere with daily social and occupational functioning or limit the implementation of psychosocial interventions. The aim of this study is to describe the trajectories of psychotropic medications in people newly diagnosed with autism according to sex and age.MethodsThis is a retrospective cohort study based on medico-administrative data from the Régie de l'assurance santé du Québec. The cohort included all people living in the province of Quebec (Canada) with a first diagnosis of autism (incident cases) recorded during hospitalisation or during a medical visit between January 2012 and December 2016 (index date: first diagnosis). Only individuals covered by the public prescription drug insurance plan one year before and one year after the index date were included. A patient was considered exposed to a drug from the date a prescription was claimed at a community pharmacy and for the time the drug was provided. However, as no information was available on inpatient drug, the drug trajectory represents the outpatient drug trajectory. The five classes of psychotropic drugs considered were: 1) anticonvulsants and mood stabilisers; 2) antipsychotics; 3) antidepressants; 4) anxiolytics/hypnotics; and 5) psychostimulants. Drug trajectories are represented using state sequence analyses.ResultsThe study cohort included 3284 people, of which 867 (26.4%) were females and 2417 (73.6%) were males. Overall, 51.6% of the cohort claimed a psychotropic medication in the year preceding diagnosis and 61.1% in the following year, with higher proportions among females and increasing with age. Psychostimulants were the most prescribed medications among people diagnosed at ages ≤12 years, while antipsychotic use increased considerably with age, becoming the most commonly prescribed medication among those diagnosed in adulthood (≥18 years), with use rates reaching as much as 80% among those diagnosed between 36 and 60 years. State sequence analyses demonstrate slight variations in the use of psychotropic medications over time, but significant variations by age category and sex.ConclusionAlthough psychosocial interventions are recognised by clinical practice guidelines as the cornerstone of interventions for people with autism, the use of psychotropic medications is widespread. This highlights a significant gap between the recommendations of these guidelines and what is observed in the real world.
Risk Factors, Symptomatology, and Predictors of Mortality Among COVID-19 Inpatients Presenting With Delirium Symptoms in a Tertiary Hospital in the Philippines
Authors: Factor Sedric John , Ly-Uson Josefina , Aligam Katrina Joy , Gelvezon Marie Angelique 
Published: August 2024

AimsThe prevalence of delirium among confirmed COVID-19 patients is around 12–33%. Delirium in COVID-19 patients is associated with worse functional outcomes; and associated with length of hospital stay, admission to ICU, and ventilator utilization. COVID-19 patients with delirium have a significantly higher risk for mortality than those who did not develop delirium. This study aimed to describe the risk factors, symptomatology, and predictors of mortality of COVID-19 patients presenting with delirium symptoms admitted between January and October 2021 to the Philippine General Hospital, a public tertiary hospital in the Philippines.MethodsMedical records of adult COVID-19 patients admitted to the Philippine General Hospital were analyzed. Descriptive statistics were used to summarize the demographic and clinical history. Univariate and multivariate logistic regression were done to determine the variables that predict mortality.ResultsOne in five (20.01%) COVID-19 patients presented with delirium; of the 1,992 medical records reviewed, 400 patients had either presented with symptoms of delirium or were diagnosed with delirium.Of the 400 patients, 36.5% were not diagnosed with delirium, only 7% were referred to Psychiatry, and 74% expired during admission. Patients referred to Psychiatry had lower mortality odds than those not referred (aOR = 0.069, p = 0.014). Before the COVID-19 pandemic, patients with psychiatric symptoms from organic causes are already less likely to be referred to psychiatrists. Furthermore, studies have shown that delirium is under-recognized among patients with COVID-19. Early referral to a psychiatrist for assessment and management may possibly be protective against mortality.Those who received midazolam had higher odds of mortality (aOR = 3.112, p = 0.001). Currently, no literature supports the association between midazolam use and mortality among COVID-19 patients with delirium; however, it is known that midazolam use puts patients at increased risk for delirium and mortality.Patients with decreased sensorium (aOR = 7.438) and decreased psychomotor activity (aOR = 3.857) had higher odds of mortality (p < 0.001). Decreased sensorium and decreased psychomotor activity are typical in patients with hypoactive delirium; hypoactive delirium is a known prognosticator for patient mortality. The only available studies on specific delirium symptomatology show that decreased sensorium and decreased psychomotor activity are common among COVID-19 patients with delirium.ConclusionTimely assessment and appropriate management are critical for COVID-19 patients with delirium symptoms, especially those at an increased risk for mortality. Clinicians dealing with COVID-19 patients presenting with delirium must be reoriented to delirium symptomatology, initial interventions, and indications for referral to psychiatrists.
BMAL1 Genetic Variation in Metabolic and Mental Health
Authors: Daudali Hamza H , Cullen Breda , Graham Nicholas , Ward Joey , Strawbridge Rona 
Published: August 2024

AimsEpidemiological studies have previously shown a link between cardiometabolic disease and severe mental illness. The extent and mechanisms behind this link are poorly understood currently but links to impairments in the stress response and cortisol regulation have been thought to play a significant role. BMAL1 is a circadian rhythm regulation gene found on chromosome 11 which has been associated with a variety of pro-inflammatory states as well as conditions such as depression, schizophrenia, type 2 diabetes mellitus and myocardial infarction. Our study aimed to investigate the genetic structure of the BMAL1 gene locus and its associations with both cardiometabolic and psychiatric traits and conditions.MethodsWe used genetic data from the UK Biobank which recruited ~500,000 participants. Of these we used a population of ~430,000 self-reported white British participants and data from a variety of questionnaires and investigations looking at severe mental illness and cardiometabolic traits. We performed association analyses using Plink 1.07 with Bonferroni correction being performed for multiple testing using a number of genetic variants. Our threshold for significance was defined as a p-value < 5.35 × 10−5. Conditional analysis was then performed to identify if there were multiple independent signals for each phenotype.ResultsBMAL1 variants were associated with BMI, diastolic, systolic blood pressure, waist-hip ratio and neuroticism score, and risk of anhedonia, major depressive disorder and risk-taking behaviour. Multiple significant independent signals were identified for BMI and waist-hip ratio. Linkage disequilibrium (LD) analysis showed significant coinheritance of specific traits which could suggest a role for BMAL1 and the encoded protein as a link between cardiometabolic and mental health traits.ConclusionThis is the first study that systematically investigated associations between the BMAL1 locus across a variety of different mental and cardiometabolic phenotypes in a population-level cohort. Our study has shown that there is a link between the BMAL1 locus and both cardiometabolic and mental health phenotypes. Further research is required to investigate the exact biological mechanism by which BMAL1 connects severe mental illness and cardiometabolic disease.
Modafinil in Post-Traumatic Brain Injury Apathy: A Sleeping Giant?
Authors: Leong Kok Keong , Mensah Seth 
Published: August 2024

AimsApathy is a complex clinical, neurobehavioural and neurobiological construct that occurs across a range of neuropsychiatric disorders. Apathy is defined as persistent, diminished motivation with impairments in goal-directed behaviour, thought, cognitive activity and emotions. Apathy negatively impacts on participation/engagement in rehabilitation and community reintegration, quality of life, and increased occupational and economic burden on families and traumatic brain injury (TBI) patients. Apathy is among the most common sequelae of TBI, with prevalence estimated to be in excess of 10%, and up to 60% in comorbid depression and apathy.There is no standard treatment for apathy, although anecdotal evidence suggests that Modafinil may be effective. Current pharmacological management strategies focus on addressing the comorbidities associated with it: e.g. acetylcholinesterase inhibitors to treat both Alzheimer's disease and apathy; dopaminergic agonists for Parkinson's disease and apathy; and antidepressants for depression and apathy.This literature review will assess the clinical evidence of Modafinil, and recommended use for treating post-TBI apathy.MethodsAn extensive search was conducted in the major databases, PsychInfo, Cochrane, Europe PMC, PubMed, EMBASE and MEDLINE, to evaluate Modafinil treatment for apathy in TBI patients. Additionally, the literature review included extra sources found in the citations. Out of 70 citations, only one was accepted for further analysis. The remaining citations were rejected due to their ineligible abstracts, absence of pharmacological interventions, inclusion of non-TBI apathy and being non-English language articles.ResultsThe accepted paper did not meet Level III evidence or better following analysis.The review however identified case reports suggesting the potential effectiveness of Modafinil in treating post-TBI apathy.Although the exact mechanism of action of Modafinil remains unclear, it is associated with improvement in working memory, attention and prefrontal-dependent cognitive function. This improvement is linked to elevated levels of extracellular dopamine, norepinephrine, serotonin, glutamate and histamine, as well as decreased GABA levels. Modafinil activates the anterior cingulate cortex, and shows positive correlation with cognitive improvement. Neuroanatomically, there is a strong association between apathy and disruption of the cortico-basal ganglia loop, involving the dorsal anterior cingulate cortex, ventral striatum and connected brain regions. Modafinil possibly has unexplored benefits in improving apathy through activation of the anterior cingulate cortex.ConclusionThere is limited empirical evidence for effective treatments for post-TBI apathy. This review emphasizes the urgent need for further research that aligns with underlying neuroanatomical pathology in order to determine the most effective psychopharmacological interventions for managing post-TBI apathy.
Review of Melatonin's Effectiveness and the Side Effects on Alzheimer's Disease
Authors: Chen Sui Yung , Khan Farooq , Talib Shoaib , Toft Suzanne 
Published: August 2024

AimsPeople who have Alzheimer's disease (AD) often experience sleep disturbances due to the nature of the illness. Melatonin has been prescribed for sleep disturbance in individuals with AD, although there is a lack of national guidelines for pharmacological care for this presentation. Prolonged sleep disturbances for individuals with AD tend to lead to poor quality of life for the individual, behavioural challenges, carers' exhaustion and potential placement breakdowns.The objective of this literature review is to determine whether the available evidence supports recommending melatonin to patients with AD for sleep, along with other benefits and adverse effects.The hypothesis for this review is that melatonin is beneficial for sleep disturbances and has neuroprotection for individuals with AD.MethodsLiterature search on the online electronic database from 2010 to November 2023, using the title of “Melatonin's effectiveness and the side effects on Alzheimer's Disease''. This literature review was done by screening the 125 searched titles. The inclusion criteria included systematic review (SR), meta-analysis, randomised controlled trial (RCT), animals and cell studies. Exclusion criteria included case studies, literature and peer reviews. A total of 12 papers are included in this review.ResultsThe three SRs, two meta-analyses and one RCT showed the potential effect of melatonin on ameriolating cognitive decline, improving cognition, quality of life and sleep qualities, with the conclusion that further studies are required. One combined meta-analysis and SR showed melatonin might be an effective treatment for mild AD. One Cochrane review showed melatonin has no evidence of improving sleep for moderate-to-severe AD.One animal study and two cellular studies showed a melatonin effect in the control progression of AD. One animal study and one cellular research study concluded that melatonin has potential treatment effects.Adverse effects were mentioned at the higher dose (10mg) with negative reaction times, sedation and confusion.ConclusionThere is a potential favourable effect of prescribing melatonin for mild to moderate AD, but there is limited evidence for prescribing it for moderate to severe AD. Furthermore, there is emerging evidence on melatonin's neuroprotective effect and potential treatment options for mild to moderate AD; further research is required for both sleep and neuroprotection in AD.
The Chicken or the Egg? Understanding the Temporal Relationship Between Severe Mental Illness and Neurological Conditions in a UK Primary Care Cohort
Authors: Burchill Ella , Rogers Jonathan , Osborn David , Hayes Joseph , Launders Naomi 
Published: August 2024

AimsA significantly higher prevalence of neurological conditions has been found both before and after a diagnosis of schizophrenia, bipolar disorder and other psychotic illnesses compared with the general population.We aimed to understand the cumulative prevalence of 16 neurological conditions in people with severe mental illness (SMI) from 5 years before to 5 years after their SMI diagnosis. We hypothesised that individual neurological conditions would have differential temporal relationships relative to SMI diagnosis.MethodsIn a longitudinal matched study, we identified a cohort of patients aged 18–100 years from Jan 1, 2000, and Dec 31, 2018, from the UK Clinical Practice Research Datalink (CPRD). Neurological conditions were classified using ICD–11 criteria into umbrella clusters of disease. Outcome of interest was a diagnosis of SMI. Each SMI patient was matched 1:4 to patients without SMI in the CPRD cohort, matching for sex, 5-year age band, primary care practice and year of practice registration. The cumulative prevalence of 16 neurological conditions was recorded cross-sectionally at 5, 3, 1 years prior to SMI diagnosis, at SMI diagnosis (index), and 1, 3 and 5 years after SMI diagnosis. Logistic regression modelling aided comparison of differential prevalence of neurological conditions, adjusting for sociodemographic variables, and with further adjustment for body mass index, smoking, alcohol and non-prescription drug use. Multiple imputation was applied in cases of missing data.ResultsWe identified 68,789 patients with SMI, matched to 274,827 controls. The median age was 40.9 years, 49.05% of the overall cohort were female (33,783 SMI patients, 134,740 controls), and the majority were of White ethnicity (35,228, 51.2% SMI patients, 125,518, 45.7% controls). The most prevalent neurological conditions across seven timepoints were cerebral palsy, cerebrovascular disease, dementia, epilepsy, multiple sclerosis, paralysis and Parkinson's disease. Conditions with the highest fully adjusted odds ratios (ORs) for SMI diagnosis were dementia 3 years after SMI diagnosis (5.32, 95% CI 4.95–5.71) and Parkinson's disease 5 years after SMI diagnosis (4.26, 95% CI 3.68–4.94).ConclusionAll 16 neurological conditions have higher prevalence in the SMI cohort compared with controls, with different prevalence patterns observed over the 10-year study period. A consistently lower OR for schizophrenia compared with other SMI warrants further exploration, as neurological conditions risk being under-recorded.A greater understanding of the temporal relationship between SMI and neurological conditions may help promote earlier diagnosis, increased screening and better holistic management of both conditions.