Fear: A conceptual analysis and philosophical therapy

Fear is a critical emotion in everyday life as it permeates many of our minor and major decisions. Explicitly or implicitly, fear is one of the emotions that most strongly shape human life. In this thesis fear and its philosophical remedies will be analysed through the work of western philosophers and thinkers selected based on their overall contributions in conceptualizing fear and suggesting therapies for reducing its more damaging effects. The study will show how Epicurus, Cicero and Seneca considered fear as the main obstacle in achieving peace of mind, and their ethical systems were primarily focused on dealing with this emotion by proposing eclectic philosophical therapies. Montaigne presented a humanist therapy of fear instrumented as a critical self-analysis. In contrast, a reductionist trend in thinking about fear emerged during the 17th century with the growth of materialistic philosophy. Thomas Hobbes reduced fear into a necessary tool for social control, whereas René Descartes demoted fear to a secondary emotion enacted by a dualist mechanism. This trend continued with William James’s conception of fear as a sensory-somatic reflex, and with Sigmund Freud’s hypothesis of a neurotic fear resulting from universal unconscious laws. I will also discuss how current neuroscience has reduced fear to decontextualized neural changes, and how the dominant trend in psychiatry has reified anxiety into arbitrary nomenclatures of unclear validity. On a completely different tack Ludwig Wittgenstein provided a broad ‘perspicuous presentation’ of fear, but his nuanced analysis has been largely ignored in philosophical studies. Overall it can be seen that, in keeping with the scientific revolution, the influential perspectives throughout the philosophical history of fear change from understandings that philosophy itself and reason are the best therapies for fear towards the medicalization of fear that is dominant today. By following these specific and diverse historical convergences, however, their criss-crossing insights and oversights, the thesis aims to enhance the conceptual understanding of fear and the variety of perspectives and therapies available for accommodating its enduring influence in our lives

High rates of parkinsonism in adults with autism

Abstract Background While it is now recognized that autism spectrum disorder (ASD) is typically a life-long condition, there exist only a handful of systematic studies on middle-aged and older adults with this condition. Methods We first performed a structured examination of parkinsonian motor signs in a hypothesis-generating, pilot study (study I) of 19 adults with ASD over 49 years of age. Observing high rates of parkinsonism in those off atypical neuroleptics (2/12, 17 %) in comparison to published population rates for Parkinson’s disease and parkinsonism, we examined a second sample of 37 adults with ASD, over 39 years of age, using a structured neurological assessment for parkinsonism. Results Twelve of the 37 subjects (32 %) met the diagnostic criteria for parkinsonism; however, of these, 29 subjects were on atypical neuroleptics, complicating interpretation of the findings. Two of eight (25 %) subjects not taking atypical neuroleptic medications met the criteria for parkinsonism. Combining subjects who were not currently taking atypical neuroleptic medications, across both studies, we conservatively classified 4/20 (20 %) with parkinsonism. Conclusions We find a high frequency of parkinsonism among ASD individuals older than 39 years. If high rates of parkinsonism and potentially Parkinson’s disease are confirmed in subsequent studies of ASD, this observation has important implications for understanding the neurobiology of autism and treatment of manifestations in older adults. Given the prevalence of autism in school-age children, the recognition of its life-long natural history, and the recognition of the aging of western societies, these findings also support the importance of further systematic study of other aspects of older adults with autism

Donepezil alone and combined with intensive language-action therapy on depression and apathy in chronic post-stroke aphasia: A feasibility study

This study explored the feasibility and effectiveness of a short-term (10-week) intervention trial using Donepezil administered alone and combined with intensive language action therapy (ILAT) for the treatment of apathy and depression in ten people with chronic post-stroke aphasia. Outcome measures were the Western Aphasia Battery and the Stroke Aphasia Depression Questionnaire-21. Structural magnetic resonance imaging and 18fluorodeoxyglucose positron emission tomography were acquired at baseline and after two endpoints (Donepezil alone and Donepezil-ILAT). The intervention was found to be feasible to implement. Large treatment effects were found. Donepezil alone and combined with ILAT reduced aphasia severity, while apathy and depression only improved with Donepezil-ILAT. Structural and functional neuroimaging data did not show conclusive results but provide hints for future research. Given these overall positive findings on feasibility, language and behavioral benefits, further studies in larger sample sizes and including a placebo-control group are indicated

Donepezil alone and combined with intensive language-action therapy on depression and apathy in chronic post-stroke aphasia: A feasibility study

This study explored the feasibility and effectiveness of a short-term (10-week) intervention trial using Donepezil administered alone and combined with intensive language action therapy (ILAT) for the treatment of apathy and depression in ten people with chronic post-stroke aphasia. Outcome measures were the Western Aphasia Battery and the Stroke Aphasia Depression Questionnaire-21. Structural magnetic resonance imaging and 18fluorodeoxyglucose positron emission tomography were acquired at baseline and after two endpoints (Donepezil alone and Donepezil-ILAT). The intervention was found to be feasible to implement. Large treatment effects were found. Donepezil alone and combined with ILAT reduced aphasia severity, while apathy and depression only improved with Donepezil-ILAT. Structural and functional neuroimaging data did not show conclusive results but provide hints for future research. Given these overall positive findings on feasibility, language and behavioral benefits, further studies in larger sample sizes and including a placebo-control group are indicated.This work was supported as an independent research grant funded by Pfizer and Eisai. The funders were not involved in the study design, collection, analysis, or interpretation of the data. The work was also supported in part by the Ministerio de Economía, Industria y Competitividad, Instituto de Salud Carlos III, Spain (under Grant: PI16/01514; MLB and GD), and the Junta de Andalucía, Spain (under Grant: P20_00501; GD). MLB has been supported by funds from the European Social Fund (FEDER). LE and FJL-G have been funded by a PhD scholarship from the Spanish Ministry of Education, Culture, and Sport under the FPU program (FPU17/04136; FJL-G: FPU17/04470). DL-B was supported by I + D + i Project Andalusia and European Union Funds (FEDER) (UMA18-FEDERJA-221) and by Ramón y Cajal Program (RYC2020-029495-I) from the Spanish Ministry of Science and Innovation. MT-P has been funded by a postdoctoral fellowship under the program Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020) (DOC_00421). FP and BM were supported by the Deutsche Forschungsgemeinschaft [Pu 97/15-1 and 15-2 to FP, Mo 697/5-2 to BM]. FP was also supported by the European Research Council [ERC-2019-ADG 883811] // Funding for open access charge: Universidad de Málaga / CBUA

Neural signatures of treatment-induced benefits in apathy and depression amongst persons with aphasia

Intensive language-action therapy (ILAT) reduces symptoms of depression in persons with aphasia (PWA) due to stroke. The neural correlates of such improvement remain unexplored. Here we evaluated apathy and depression in PWA receiving treatment with the cholinesterase inhibitor donepezil (DP) alone and combined with ILAT as well as the brain changes promoted by these interventions. Ten PWA with chronic left perisylvian strokes participated in a 10-week open-label pilot study. They received DP alone (wk 0-8) and thereafter combined with ILAT (wk 8-10 30 hours, wks 8-10). Structural MRI and resting state [18]fluorodeoxyglucose PET (18FDG-PET) were acquired for at 3 time-points in order to measure grey matter density (Voxel-based morphometry, VBM) and metabolic changes. The primary outcome measures were: Aphasia Quotient of the Western Aphasia Battery (AQ-WAB), Communicative Activity Log (CAL), Stroke Aphasic Depression Questionnaire (SADQ), and Stroke and Aphasia Quality of Life Scale-39 (SAQoL-39). The 21-item SADQ was used to examine apathy (7 items) and depression (14 items). Significant improvements with DP alone and under DP-ILAT were seen in AQ-WAB, CAL and SAQoL-39. Improvements in symptoms of apathy and depression were observed when comparing DP-ILAT with baseline. 18FDG-PET analysis revealed that DP alone induced significant increments in metabolic activity in cortical and subcortical areas that correlated with improvement in apathetic and depressive symptoms. VBM analyses revealed that DP alone and combined DP-ILAT induced increases in grey matter density in areas of the right hemisphere previously associated to improvements in apathy and depression. In conclusion, treatment with DP alone and combined with ILAT improved aphasia, communication and quality of life as well as associated symptoms of apathy and depression by modulating regions innervated by the left medial, right lateral and brainstem cholinergic pathways.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Sertraline for anxiety in adults with a diagnosis of autism (STRATA) : study protocol for a pragmatic, multicentre, double-blind, placebo-controlled randomised controlled trial

Background: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population are not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and to quantify any adverse effects. Methods: STRATA is a two-parallel group, multi-centre, pragmatic, double-blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥ 10 at screening will be randomised 1:1 to either 25 mg sertraline or placebo, with subsequent flexible dose titration up to 200 mg. The primary outcome is GAD-7 scores at 16 weeks post-randomisation. Secondary outcomes include adverse effects, proportionate change in GAD-7 scores including 50% reduction, social anxiety, obsessive-compulsive symptoms, panic attacks, repetitive behaviours, meltdowns, depressive symptoms, composite depression and anxiety, functioning and disability and quality of life. Carer burden will be assessed in a linked carer sub-study. Outcome data will be collected using online/paper methods via video call, face-to-face or telephone according to participant preference at 16, 24 and 52 weeks post-randomisation, with brief safety checks and data collection at 1–2, 4, 8, 12 and 36 weeks. An economic evaluation to study the cost-effectiveness of sertraline vs placebo and a QuinteT Recruitment Intervention (QRI) to optimise recruitment and informed consent are embedded within the trial. Qualitative interviews at various times during the study will explore experiences of participating and taking the trial medication. Discussion: Results from this study should help autistic adults and their clinicians make evidence-based decisions on the use of sertraline for managing anxiety in this population. Trial registration: ISRCTN, ISRCTN15984604. Registered on 08 February 2021. EudraCT 2019-004312-66. ANZCTR ACTRN12621000801819. Registered on 07 April 2021