1,204 results on '"Paul, Willner"'
Search Results
2. Reliability of the chronic mild stress model of depression: A user survey
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Paul Willner
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Depression ,Chronic mild stress ,Reproducibility ,Reliability ,Sucrose intake ,Rat ,Mouse ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 ,Neurophysiology and neuropsychology ,QP351-495 - Abstract
The chronic mild stress (CMS) model of depression is considered by many to be the animal model of depression that has the greatest validity and translational potential, but it has often been criticized for a perceived lack of reliability. The aims of this study were to establish the extent to which the procedure is reproducible, and to identify experimental variables relevant to its reliability. Because failures to replicate frequently remain unpublished, a survey methodology was used. A questionnaire was circulated to 170 labs identified from a PubMed search as having published a CMS study in the years 2010 or 2015 (with no selection in respect of the results reported). Responses were returned by 71 (42%) of the recipients, followed by further correspondence with some of them. Most of the respondents (n = 53: 75%) reported that the CMS procedure worked reliably in their hands. Of the others, 15 (21%) reported that the procedure was usually reliable, but not always (n = 9: 13%) or not for all measures (n = 6: 8%). Only three respondents (4%) reported being unable to reproduce the characteristic effects, two of whom may be using an insufficient duration of CMS exposure. A series of analyses compared the 75% of ‘reliable’ labs with the 25% of ‘less reliable’ labs on a range of experimenter, subject, stress and outcome variables. Few if any significant differences between these two samples were identified, possibly because of the small size and diversity of the ‘less reliable’ sample. Two other limitations of the study include the (unavoidable) omission of labs that may have worked with the model but not published their data, and the use of ad hoc measures to compare the severity of different stress regimes. The results are discussed in relation to relevant published observations. It is concluded that CMS is in fact a rather robust model, but the factors that result in a less effective implementation in a minority of laboratories remain to be firmly established.
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- 2017
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3. The chronic mild stress (CMS) model of depression: History, evaluation and usage
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Paul Willner
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Depression ,Chronic mild stress ,Validity ,Reliability ,Neurobiology of stress ,Antidepressant ,Hippocampus ,Prefrontal cortex ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 ,Neurophysiology and neuropsychology ,QP351-495 - Abstract
Now 30 years old, the chronic mild stress (CMS) model of depression has been used in >1300 published studies, with a year-on-year increase rising to >200 papers in 2015. Data from a survey of users show that while a variety of names are in use (chronic mild/unpredictable/varied stress), these describe essentially the same procedure. This paper provides an update on the validity and reliability of the CMS model, and reviews recent data on the neurobiological basis of CMS effects and the mechanisms of antidepressant action: the volume of this research may be unique in providing a comprehensive account of antidepressant action within a single model. Also discussed is the use of CMS in drug discovery, with particular reference to hippocampal and extra-hippocampal targets. The high translational potential of the CMS model means that the neurobiological mechanisms described may be of particular relevance to human depression and mechanisms of clinical antidepressant action.
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- 2017
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4. Models of Affective Illness: Chronic Mild Stress in the Rat
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Mariusz Papp and Paul Willner
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Medical Laboratory Technology ,General Immunology and Microbiology ,General Neuroscience ,Health Informatics ,General Pharmacology, Toxicology and Pharmaceutics ,General Biochemistry, Genetics and Molecular Biology - Published
- 2023
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5. Some observations on remote delivery of eye‐movement desensitisation and reprocessing to people with intellectual disabilities
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Gemma Unwin, Biza Stenfert‐Kroese, Gemma Rogers, Sophie Swain, Steve Hiles, Clair Clifford, Derek Farrell, and Paul Willner
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Health (social science) ,Public Health, Environmental and Occupational Health - Published
- 2023
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6. The pharmacology of executive functioning: part 2: research reports
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Jack, Bergman, Louk, Vanderschuren, Ellenbroek, Bart, and Paul, Willner
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- 2018
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7. Perspectives for therapy of treatment‐resistant depression
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Wiesław Jerzy Cubała, Paul Willner, Lukasz Swiecicki, Mariusz Papp, and Adrian Newman-Tancredi
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Pharmacology ,Deep brain stimulation ,Depression ,business.industry ,medicine.medical_treatment ,medicine.disease ,Bioinformatics ,Antidepressive Agents ,Somatic psychology ,Depressive Disorder, Treatment-Resistant ,Mood disorders ,medicine ,Animals ,Antidepressant ,Ketamine ,Psychopharmacology ,business ,Treatment-resistant depression ,Depression (differential diagnoses) ,medicine.drug - Abstract
A high proportion of depressed patients fail to respond to antidepressant drug treatment. Treatment-resistant depression (TRD) is a major challenge for the psychopharmacology of mood disorders. Only in the past decade have novel treatments, including deep brain stimulation (DBS) and ketamine, been discovered that provide rapid and sometimes prolonged relief to a high proportion of TRD sufferers. In this review, we consider the current status of TRD from four perspectives: the challenge of developing an appropriate regulatory framework for novel rapidly acting antidepressants; the efficacy of non-pharmacological somatic therapies; the development of an animal model of TRD and its use to understand the neural basis of antidepressant non-response; and the potential for rapid antidepressant action from targets (such as 5-HT1A receptors) beyond the glutamate receptor.
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- 2021
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8. AMPA receptors mediate the pro-cognitive effects of electrical and optogenetic stimulation of the medial prefrontal cortex in antidepressant non-responsive Wistar–Kyoto rats
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Magdalena Lason, Mariusz Papp, Paul Willner, Piotr Gruca, Ewa Litwa, and W. Solecki
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Male ,Deep Brain Stimulation ,medicine.medical_treatment ,Venlafaxine ,Stimulation ,Hippocampus ,Rats, Inbred WKY ,Depressive Disorder, Treatment-Resistant ,Chronic mild stress ,0302 clinical medicine ,venlafaxine ,Pharmacology (medical) ,AMPA receptors ,Prefrontal cortex ,optogenetic stimulation ,Behavior, Animal ,Venlafaxine Hydrochloride ,Wistar–Kyoto rat ,Original Papers ,deep brain stimulation ,Psychiatry and Mental health ,Antidepressive Agents, Second-Generation ,Antidepressant ,medicine.drug ,Ampakine ,Deep brain stimulation ,medicine.drug_class ,Wistar-Kyoto rat ,Prefrontal Cortex ,ampakine ,AMPA receptor ,Optogenetics ,behavioral disciplines and activities ,03 medical and health sciences ,medicine ,Animals ,Excitatory Amino Acid Agents ,Receptors, AMPA ,Rats, Wistar ,Pharmacology ,business.industry ,chronic mild stress ,Rats ,030227 psychiatry ,Disease Models, Animal ,nervous system ,business ,Neuroscience ,medial prefrontal cortex ,Stress, Psychological ,030217 neurology & neurosurgery - Abstract
Background: The chronic mild stress (CMS) procedure is a widely used animal model of depression, and its application in Wistar–Kyoto (WKY) rats has been validated as a model of antidepressant-refractory depression. While not responding to chronic treatment with antidepressant drugs, WKY rats do respond to acute deep brain stimulation (DBS) of the medial prefrontal cortex (mPFC). In antidepressant-responsive strains there is evidence suggesting a role for AMPA subtype of glutamate receptor in the action mechanism of both antidepressants and DBS. Methods: Animals were subjected to CMS for 6 to 8 weeks; sucrose intake was monitored weekly and novel object recognition (NOR) test was conducted following recovery from CMS. Wistars were treated chronically with venlafaxine (VEN), while WKY were treated acutely with either DBS, optogenetic stimulation (OGS) of virally-transduced (AAV5-hSyn-ChR2-EYFP) mPFC or ventral hippocampus, or acute intra-mPFC injection of the AMPA receptor positive allosteric modulator CX-516. The AMPA receptor antagonist NBQX was administered, at identical sites in mPFC, immediately following the exposure trial in the NOR. Results: Sucrose intake and NOR were suppressed by CMS, and restored by VEN in Wistars and by DBS, OGS, or CX-516 in WKY. However, OGS of the ventral hippocampal afferents to mPFC was ineffective. A low dose of NBQX selectively blocked the procognitive effect of VEN, DBS and OGS. Conclusions: These results suggest that activation of AMPA receptors in the mPFC represents a common pathway for the antidepressant effects of both conventional (VEN) and novel (DBS, OGS) antidepressant modalities, in both antidepressant responsive (Wistar) and antidepressant-resistant (WKY) rats.
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- 2020
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9. The effect on and experience of families with a member who has Intellectual and Developmental Disabilities of the COVID-19 pandemic in the UK: developing an investigation
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Paul Willner, Vivien Cooper, Peter E. Langdon, Biza Stenfert Kroese, Glynis H. Murphy, and John Rose
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030506 rehabilitation ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,05 social sciences ,Points of View ,03 medical and health sciences ,Psychiatry and Mental health ,Family medicine ,Political science ,Pandemic ,medicine ,Developmental and Educational Psychology ,0501 psychology and cognitive sciences ,0305 other medical science ,050104 developmental & child psychology - Abstract
The coronavirus disease 2019 (COVID-19) pandemic is the most pressing issue we now face and has had major implications on the way we all live our lives. There are clearly specific issues faced by p...
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- 2022
10. Optogenetic stimulation of transmission from prelimbic cortex to nucleus accumbens core overcomes resistance to venlafaxine in an animal model of treatment-resistant depression
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Mariusz Papp, Piotr Gruca, Ewa Litwa, Magdalena Lason, and Paul Willner
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Pharmacology ,Biological Psychiatry - Abstract
Our earlier study demonstrated that repeated optogenetic stimulation of afferents from ventral hippocampus (vHIP) to the prelimbic region of medial prefrontal cortex (mPFC) overcame resistance to antidepressant treatment in Wistar-Kyoto (WKY) rats. These results suggested that antidepressant resistance may result from an insufficiency of transmission from vHIP to mPFC. Here we examined whether similar effects can be elicited from major output of mPFC; the pathway from to nucleus accumbens core (NAc).WKY rats were subjected to Chronic Mild Stress and were used in two sets of experiments: 1) they were treated acutely with optogenetic stimulation of afferents to NAc core originating from the mPFC, and 2) they were treated with chronic (5 weeks) venlafaxine (10 mg/kg) and/or repeated (once weekly) optogenetic stimulation of afferents to NAc originating from either mPFC or vHIP.Chronic mild stress procedure decreased sucrose intake, open arm entries on elevated plus maze, and novel object recognition test. Acute optogenetic stimulation of the mPFC-NAc and vHIP-NAc pathways had no effect in sucrose or plus maze tests, but increased object recognition. Neither venlafaxine nor mPFC-NAc optogenetic stimulation alone was effective in reversing the effects of CMS, but the combination of chronic antidepressant and repeated optogenetic stimulation improved behaviour on all three measures.The synergism between venlafaxine and mPFC-NAc optogenetic stimulation supports the hypothesis that the mechanisms of non-responsiveness of WKY rats involves a failure of antidepressant treatment to restore transmission in the mPFC-NAc pathway. Together with earlier results, this implicates insufficiency in a vHIP-mPFC-NAc circuit in non-responsiveness to antidepressant drugs.
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- 2023
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11. Occupational stress, coping and wellbeing among registered psychologists working with people with intellectual disabilities during the COVID-19 pandemic in the United Kingdom
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Peter E. Langdon, Paul Willner, Magdalena Marczak, and Clair Clifford
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2019-20 coronavirus outbreak ,medicine.medical_specialty ,Coping (psychology) ,Coronavirus disease 2019 (COVID-19) ,Stressor ,education ,BF ,behavioral disciplines and activities ,Mental health ,Education ,HV ,Arts and Humanities (miscellaneous) ,Learning disability ,Pandemic ,medicine ,sense organs ,Occupational stress ,medicine.symptom ,skin and connective tissue diseases ,Psychiatry ,Psychology ,human activities ,RA ,General Psychology ,RC - Abstract
Objectives: To characterise the changes at work experienced by psychologists working with people with intellectual disabilities during the pandemic and whether these changes, stressors and aspects of working life were associated with mental wellbeing and occupational stress.\ud Methods: Ninety-seven psychologists completed an online survey. Free text comments were analysed using thematic analysis and triangulated with our quantitative findings.\ud Results: Occupational stress, learning new roles, demands at home, and changes due to COVID-19 were associated with poorer mental wellbeing, while uncertainty about the role, a shortage of personal protective equipment, and poorer mental wellbeing were associated with occupational\ud stress. Two main themes emerged during the thematic analysis: being human and being an employee, and triangulation revealed agreement.\ud Conclusions: The wellbeing and occupational stress of psychologists working with people with intellectual disabilities have been affected during the pandemic. It is of note that almost a quarter of our sample reported having been redeployed.
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- 2022
12. Optogenetic stimulation of medial prefrontal cortex excites GABAergic cells in the nucleus accumbens and hippocampus of Wistar-Kyoto rats exposed to chronic mild stress
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Mariusz Papp, Piotr Gruca, Magdalena Lason, Ewa Litwa, Wojciech Solecki, and Paul Willner
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Pharmacology ,GABAergic neurons ,nucleus accumbens ,hippocampus ,Wistar-Kyoto rat ,chronic mild stress ,Prefrontal Cortex ,confocal microscopy ,glutamatergic neurons ,Hippocampus ,Rats, Inbred WKY ,Antidepressive Agents ,Nucleus Accumbens ,Rats ,Optogenetics ,prelimbic cortex ,Animals ,optogenetic stimulation - Abstract
High frequency optogenetic stimulation (OGS) of prelimbic cortex (PLC) has been reported to exert antidepressant-like effects in the chronic mild stress model of depression in Wistar Kyoto (WKY) rats, which are non-responsive to antidepressant drugs. Here we have examined the effect of OGS on activity in the PLC and in two other regions implicated in depression, the nucleus accumbens (NAc) and hippocampus (HPC).OGS was applied to the PLC of WKY rats using the same stress schedule, and the identical placement, virus infection and stimulation parameters, used in the earlier behavioural experiments. Confocal microscopy was used to identify cells co-expressing the immediate early gene c-Fos and markers of GABAergic (GAD) and glutamatergic (CaMKII) neurons.Stress decreased sucrose intake, which was restored by OGS. Stress also caused an overall decrease in Fos expression in the structures examined. In stressed animals, but not in non-stressed controls, OGS in mPFC increased the number of FosWe conclude that OGS of PLC has a net excitatory effect on outputs from the PLC, leading to an overall inhibitory effect in structures innervated (NAc and HPC).
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- 2021
13. Editorial: The Behavioural Pharmacology of Cannabinoids
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Louk, Vanderschuren, Emily, Jutkiewicz, Paul, Willner, and Bart, Ellenbroek
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Pharmacology ,Psychiatry and Mental health ,Cannabinoids ,Taverne ,Cannabis - Published
- 2022
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14. Genomic Screening of Wistar and Wistar-Kyoto Rats Exposed to Chronic Mild Stress and Deep Brain Stimulation of Prefrontal Cortex
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Piotr Gruca, Mariusz Papp, Agata Faron-Górecka, M. Kusmider, and Paul Willner
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Male ,0301 basic medicine ,medicine.medical_specialty ,Deep brain stimulation ,Deep Brain Stimulation ,medicine.medical_treatment ,EGR1 ,Prefrontal Cortex ,Hippocampus ,Rats, Inbred WKY ,Genomic screening ,03 medical and health sciences ,0302 clinical medicine ,Mild stress ,Internal medicine ,Gene expression ,Animals ,Medicine ,Rats, Wistar ,Prefrontal cortex ,Depression ,business.industry ,General Neuroscience ,Genomics ,Antidepressive Agents ,Rats ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Behavior Rating Scale ,Antidepressant ,business ,Stress, Psychological ,030217 neurology & neurosurgery - Abstract
Stress, a major precipitant of depression, and antidepressants have major impact on synaptic integrity and plasticity in brain areas, such as hippocampus (HPC) and prefrontal cortex (PFC). We have recently shown that, unlike Wistar rats, rats of the Wistar-Kyoto (WKY) strain fail to respond to chronic antidepressant treatment after exposure to chronic mild stress (CMS) procedure. However, deep brain stimulation (DBS) of PFC was effective in both strains. We aimed to identify genes that were affected by CMS, to determine whether their expression was normalized by DBS, and to establish whether common changes could be identified in antidepressant responsive (Wistar) and antidepressant-resistant (WKY) strains. Male Wistar and WKY rats were exposed chronically to CMS then treated acutely with DBS. A battery of behavioural tests was used to monitor recovery, followed by TaqMan screening of a panel of genes known to be involved in stress and antidepressant action. WKY showed over-expression of five genes in dorsal HPC and under-expression of seven genes in ventral HPC. Expression of three genes, Egr1, Htr7 and Mmp9 was decreased by CMS and normalized by DBS in the ventral HPC of Wistar rats. Some other changes in gene expression were identified in dorsal HPC and PFC, particularly in Wistars, that were not normalized by DBS. No effects were identified that were common to both Wistars and WKY. The difference between Wistars and WKY in the balance of overall gene expression in HPC may be relevant to the resistance of WKY rats to antidepressant drug treatment.
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- 2019
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15. Assessment of Anger and Aggression
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Paul Willner, Andrew Jahoda, and Kenneth Macmahon
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Buss–Perry Aggression Questionnaire ,Aggression ,media_common.quotation_subject ,medicine ,medicine.symptom ,Anger ,Risk assessment ,Psychology ,Modified Overt Aggression Scale ,Clinical psychology ,media_common - Published
- 2019
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16. Functional lateralization in the prefrontal cortex of dopaminergic modulation of memory consolidation
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Monika Niemczyk, Paul Willner, Magdalena Lason, Mariusz Papp, and Piotr Gruca
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Male ,Agonist ,medicine.medical_specialty ,medicine.drug_class ,Dopamine ,Prefrontal Cortex ,Functional Laterality ,Lateralization of brain function ,Receptors, Dopamine ,03 medical and health sciences ,0302 clinical medicine ,Quinpirole ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Receptor ,Prefrontal cortex ,Memory Consolidation ,Pharmacology ,Receptors, Dopamine D2 ,business.industry ,Dopaminergic Neurons ,Receptors, Dopamine D1 ,Antagonist ,Rats ,030227 psychiatry ,Psychiatry and Mental health ,Endocrinology ,Dopamine Agonists ,Dopamine Antagonists ,Memory consolidation ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
There is increasing evidence of functional lateralization within the rat brain. Here, we have examined the lateralization of dopamine (DA) function in the medial prefrontal cortex (PFC) in relation to memory consolidation in the novel object recognition test (NOR). Male Wistar rats received single bilateral or unilateral injections into prelimbic-PFC of agonists (SKF81297; 0.2 µg, quinpirole; 1 µg, SB277,011; 0.5 µg) and antagonists (SCH23390; 3 µg, L-741,626; 1 µg, 7-OH-DPAT; 3 µg) at DA D1, D2, or D3 receptors, immediately following the exposure trial in the NOR, and were tested either 1 or 24 h later for discrimination between a novel and a familiar object. As previously reported, bilateral injection of a D1 antagonist (SCH23390, 3 µg/side), a D2 antagonist (L-741,626, 1 µg/side) or a D3 agonist (7-OH-DPAT, 3 µg/side) impaired NOR at 1 h, while a D1 agonist (SKF81297, 0.2 µg/side), a D2 agonist (quinpirole, 1 µg/side) or a D3 antagonist (SB277,011, 0.5 µg/side) improved NOR at 24 h. The same effects were seen with left-sided unilateral injections. No effects were seen with right-sided unilateral injections. Endogenous DA release in the prelimbic-PFC promotes memory consolidation in the NOR, but only on the left side of the brain.
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- 2019
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17. The Experiences of Carers of Adults With Intellectual Disabilities During the First COVID‐19 Lockdown Period
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Gemma Rogers, Steve Hiles, Clair Clifford, Varsha Patel, John Rose, Gisela Perez‐Olivas, Vivien Cooper, Paul Willner, Peter E. Langdon, Glynis H. Murphy, and Biza Stenfert Kroese
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medicine.medical_specialty ,Coping (psychology) ,Health (social science) ,Coronavirus disease 2019 (COVID-19) ,media_common.quotation_subject ,carers ,HM ,lockdown ,HV ,COVID‐19 ,Intellectual disability ,Pandemic ,medicine ,Psychiatry ,media_common ,Public Health, Environmental and Occupational Health ,parents ,Original Articles ,medicine.disease ,Mental health ,intellectual disability ,Original Article ,Psychological resilience ,Thematic analysis ,Psychology ,RA ,Period (music) ,RC - Abstract
Background:\ud The recent COVID-19 pandemic led to widespread international restrictions, severely impacting on health and social care services. For many individuals with an intellectual disability (ID) this meant reduced access to services and support for them and their carers.\ud \ud Aim:\ud The aim of this study was to gain insight into the ways parents of adults with ID coped during the first 2020 lockdown period.\ud \ud Methods:\ud Eight parents of adults with ID were interviewed. The recordings of these interviews were subjected to a thematic analysis.\ud \ud Results:\ud Four main themes were identified: powerless and unappreciated; coping under lockdown; support; and the impact of lockdown on well-being.\ud \ud Conclusions:\ud The parents of adults with ID who made up our sample reported that they received little support from services and experienced a sense of powerlessness. Nevertheless, they were open to accepting support from family and friends and showed remarkable resilience. These findings are discussed in the light of the Willner et al. (2020) survey results on parental mental health and coping, and suggestions for future service provision during pandemic conditions are proposed.
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- 2021
18. The experiences of mothers of children and young people with intellectual disabilities during the first COVID‐19 lockdown period
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Clair Clifford, Steve Hiles, Paul Willner, Vivien Cooper, Glynis H. Murphy, Gisela Perez‐Olivas, Biza Stenfert Kroese, Varsha Patel, Peter E. Langdon, John Rose, and Gemma Rogers
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Coronavirus disease 2019 (COVID-19) ,Adolescent ,RJ ,Service provision ,Mothers ,Survey result ,young people ,Education ,Developmental psychology ,Social support ,HV ,children ,Intellectual Disability ,HQ ,Developmental and Educational Psychology ,Parental coping ,Humans ,Applied research ,Child ,Covid‐19 ,SARS-CoV-2 ,COVID-19 ,Original Articles ,Communicable Disease Control ,Original Article ,Female ,Thematic analysis ,intellectual disabilities ,Psychology ,RA ,caring responsibility ,Period (music) ,RC - Abstract
Background:\ud Recent COVID‐19 lockdown restrictions resulted in reduced access to educational, professional and social support systems for children with intellectual disabilities and their carers.\ud \ud Aim:\ud The aim of this study was to gain insight into the ways mothers of children with intellectual disabilities coped during the first 2020 lockdown period.\ud \ud Methods:\ud Eight mothers of children with intellectual disabilities were interviewed. The recordings of these interviews were subjected to a thematic analysis.\ud \ud Results:\ud Three main themes were identified: carrying the burden; a time of stress; and embracing change and looking to the future.\ud \ud Conclusions:\ud All mothers experienced increased burden and stress. However, some also described some positive impact of lockdown conditions on them as well as on their child's well‐being and behaviour. These findings are discussed in the light of the (Journal of Applied Research in Intellectual Disabilities, 33, 2020, 1523) survey results on parental coping and suggestions for future service provision during pandemic conditions are proposed.\ud \ud
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- 2021
19. Insufficiency of ventral hippocampus to medial prefrontal cortex transmission explains antidepressant non-response
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W. Solecki, Ewa Litwa, Paul Willner, Magdalena Lason, Piotr Gruca, and Mariusz Papp
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Male ,Hippocampus ,Ventral hippocampus ,Prefrontal Cortex ,Venlafaxine ,Rats, Inbred WKY ,venlafaxine ,medicine ,Animals ,Pharmacology (medical) ,Prefrontal cortex ,Maze Learning ,Brain function ,optogenetic stimulation ,Pharmacology ,WKY rat ,business.industry ,Depression ,Venlafaxine Hydrochloride ,Original Papers ,Antidepressive Agents ,Rats ,Optogenetics ,Psychiatry and Mental health ,Disease Models, Animal ,nervous system ,Antidepressant ,business ,Neuroscience ,ventral hippocampus ,Stress, Psychological ,medial prefrontal cortex ,medicine.drug - Abstract
Background: There is extensive evidence that antidepressant drugs restore normal brain function by repairing damage to ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC). While the damage is more extensive in hippocampus, the evidence of treatments, such as deep brain stimulation, suggests that functional changes in prefrontal cortex may be more critical. We hypothesized that antidepressant non-response may result from an insufficiency of transmission from vHPC to mPFC. Method: Antidepressant non-responsive Wistar Kyoto (WKY) rats were subjected to chronic mild stress (CMS), then treated with chronic daily administration of the antidepressant drug venlafaxine (VEN) and/or repeated weekly optogenetic stimulation (OGS) of afferents to mPFC originating from vHPC or dorsal HPC (dHPC). Results: As in many previous studies, CMS decreased sucrose intake, open-arm entries on the elevated plus maze (EPM), and novel object recognition (NOR). Neither VEN nor vHPC–mPFC OGS alone was effective in reversing the effects of CMS, but the combination of chronic VEN and repeated OGS restored normal behaviour on all three measures. dHPC–mPFC OGS restored normal behaviour in the EPM and NOR test irrespective of concomitant VEN treatment, and had no effect on sucrose intake. Conclusions: The synergism between VEN and vHPC–mPFC OGS supports the hypothesis that the antidepressant non-responsiveness of WKY rats results from a failure of antidepressant treatment fully to restore transmission in the vHPC–mPFC pathway.
- Published
- 2021
20. The prevalence of mental health difficulties in a sample of prisoners in Trinidadian prisons referred for anger management
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Paul Willner, Tony Bastick, Gerard Hutchinson, and John Rose
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050103 clinical psychology ,medicine.medical_specialty ,Anger management ,medicine.medical_treatment ,media_common.quotation_subject ,Population ,location.country ,Prison ,Sample (statistics) ,Trinidadian ,behavioral disciplines and activities ,Pathology and Forensic Medicine ,03 medical and health sciences ,location ,0302 clinical medicine ,mental disorders ,medicine ,0501 psychology and cognitive sciences ,education ,Psychiatry ,Practical implications ,Applied Psychology ,media_common ,education.field_of_study ,Prison population ,05 social sciences ,virus diseases ,social sciences ,Mental health ,030227 psychiatry ,Psychiatry and Mental health ,Psychology ,Law - Abstract
Purpose The purpose of this paper is to evaluate the prevalence of mental health disorder symptoms in a sample of prisoners in Trinidadian prisons who volunteered to attend anger management groups. Design/methodology/approach A survey was conducted using the 90-item Symptom Check-List revised (SCL-90-R) which was administered to prisoners in groups within the prison system. In total 132 prisoners (about 9 per cent of the prison population) completed the measure. The effect sizes of prisoners’ similarities to a psychiatric inpatient group and their differences from a non-patient group were used to identify symptoms most indicative of pathology in these prisoners. Findings The results on the SCL-90-R indicate that this group of prisoners (77.3 per cent male) had scores of psychiatric symptomatology that were much closer to a psychiatric inpatient population rather than to a general community population. Practical implications These results suggest there may be unmet psychiatric need among the population served by the prison services in Trinidad. It is not known how this sample differs from the general prison population. However, the unmet psychiatric need in this specific population suggests that a greater mental health focus in health services within prisons is to be considered to meet these needs. Originality/value These data suggest that there are significant mental health issues for some prisoners in Trinidad and possibly more generally in similar prison systems within the Caribbean and this may have significant implications for the treatment of prisoners and the delivery of mental health services in these prisons.
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- 2018
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21. Rapid antidepressant effects of deep brain stimulation of the pre-frontal cortex in an animal model of treatment-resistant depression
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Monika Niemczyk, Katarzyna Tota-Glowczyk, Piotr Gruca, Mariusz Papp, Paul Willner, Ewa Litwa, and Magdalena Lason
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Male ,Imipramine ,Deep brain stimulation ,Deep Brain Stimulation ,medicine.medical_treatment ,Prefrontal Cortex ,Venlafaxine ,Citalopram ,Depressive Disorder, Treatment-Resistant ,03 medical and health sciences ,0302 clinical medicine ,Animal model ,Animals ,Medicine ,Pharmacology (medical) ,Rats, Wistar ,Prefrontal cortex ,Pharmacology ,Behavior, Animal ,business.industry ,Venlafaxine Hydrochloride ,medicine.disease ,Antidepressive Agents ,Rats ,030227 psychiatry ,Disease Models, Animal ,Psychiatry and Mental health ,Antidepressant ,business ,Treatment-resistant depression ,Neuroscience ,Stress, Psychological ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background: A significant proportion of depressed patients fail to respond to treatment with antidepressant drugs. Such patients might nonetheless respond to deep brain stimulation of the prefrontal cortex. Deep brain stimulation has also been shown to normalize behaviour in the chronic mild stress (CMS) model of depression. However, these studies have involved animals that are in general treatment responsive. Thus, this is not the ideal situation in which to investigate how deep brain stimulation is effective where antidepressant drugs are not. Aims: Here, we studied the behavioural effects of deep brain stimulation in treatment-resistant animals. Methods: Wistar rats were exposed to chronic mild stress and concurrent treatment with saline or one of three antidepressant drugs, imipramine, citalopram and venlafaxine. Individuals were selected from the CMS-exposed drug-treated groups that had failed to increase their sucrose intake by week 5 of drug treatment. All animals were then implanted with deep brain stimulation electrodes in the ventro-medial prefrontal cortex, and tested for sucrose intake and in the elevated plus maze and novel object recognition test, following 2 × 2 h of deep brain stimulation. Results: The selected drug-treated animals were found to be antidepressant-resistant in all three tests. With a single exception (sucrose intake in imipramine-treated animals), deep brain stimulation reversed the anhedonic, anxiogenic and dyscognitive effects of CMS in all four conditions, with no significant differences between saline- and drug-treated animals. Conclusions: These data provide a proof of principle that deep brain stimulation of the prefrontal cortex can be effective in a rat model of resistance to chronic antidepressant treatment, replicating the clinical effect of deep brain stimulation in treatment-resistant depression.
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- 2018
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22. Effects on brain-derived neurotrophic factor signalling of chronic mild stress, chronic risperidone and acute intracranial dopamine receptor challenges
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Joanna Solich, Marta Szlachta, Paul Willner, Agata Faron-Górecka, Piotr Gruca, Ewa Litwa, Katarzyna Tota-Glowczyk, Monika Niemczyk, M. Kusmider, Mariusz Papp, and Magdalena Lason-Tyburkiewicz
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Male ,0301 basic medicine ,Agonist ,medicine.medical_specialty ,Quinpirole ,medicine.drug_class ,Dopamine Agents ,Prefrontal Cortex ,Hippocampus ,Receptors, Dopamine ,03 medical and health sciences ,0302 clinical medicine ,Dopamine ,Neurotrophic factors ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Rats, Wistar ,Pharmacology ,Brain-derived neurotrophic factor ,business.industry ,Brain-Derived Neurotrophic Factor ,Antagonist ,Electroencephalography ,Benzazepines ,Risperidone ,Rats ,Disease Models, Animal ,Psychiatry and Mental health ,030104 developmental biology ,Endocrinology ,nervous system ,Dopamine receptor ,business ,Stress, Psychological ,030217 neurology & neurosurgery ,Antipsychotic Agents ,Signal Transduction ,medicine.drug - Abstract
We have previously reported the effects of intracranial injections of dopamine D1, D2 and D3 ligands in animals subjected to the Novel Object Recognition (NOR) test following exposure to chronic mild stress (CMS) and chronic treatment with risperidone (RSP). Here, we present some molecular biological data from the same animals. It was predicted that brain-derived neurotrophic factor (BDNF) signalling in the prefrontal cortex (PFC) would reflect behavioural performance, implying an increase following acute administration of a D2 agonist or a D3 antagonist, blockade of this effect by CMS and its restoration by chronic RSP. In separate cohorts, animals were injected within the PFC or the hippocampus (HPC) with either the D1 agonist SKF-81297, the D2 agonist quinpirole or the D3 antagonist SB-277,011, following exposure to control conditions or CMS and chronic treatment with saline or RSP. Intracranial injections followed an exposure trial in the NOR test, with a retention trial 24 h later. Immediately afterwards, the animals were killed and expression of BDNF and TRKβ protein, and their respective mRNAs, was measured in PFC and HPC samples. CMS decreased the expression of TRKβ in both PFC and HPC. Several effects associated with intracranial injection were noted, but they were inconsistent and unrelated to CMS exposure. The effects of CMS on TRKβ are consistent with a decrease in BDNF signalling, albeit that expression of BDNF itself did not change significantly. There was no evidence for an involvement of the BDNF-TRKβ system in responses to RSP or dopamine ligands in animals exposed to CMS. However, there was a 24 h delay between the intracranial injection and tissue harvesting, meaning that brief early drug effects could have been missed.
- Published
- 2018
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23. The behavioural pharmacology of stress-related disorders
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Jack Bergman, Louk J. M. J. Vanderschuren, and Paul Willner
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Pharmacology ,Behavioural pharmacology ,business.industry ,Mental Disorders ,Stress-related disorders ,MEDLINE ,Behavioural sciences ,Pharmacological Phenomena ,Psychiatry and Mental health ,Stress, Physiological ,Taverne ,Animals ,Humans ,Medicine ,business ,Behavioral Sciences ,Clinical psychology - Published
- 2019
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24. Translational Research in Behavioural Pharmacology
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Paul Willner, Emily Jutkiewicz, Jack Bergman, and Louk J. M. J. Vanderschuren
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Translational Research, Biomedical ,Pharmacology ,Cognitive science ,Behavior ,Psychiatry and Mental health ,Behavioural pharmacology ,Behavior, Animal ,Taverne ,Animals ,Humans ,Translational research ,Psychology - Published
- 2021
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25. Sleep does not cause false memories on a story-based test of suggestibility
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Elaine van Rijn, Mark Blagrove, Hazel McMurtrie, Neil Carter, and Paul Willner
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Adult ,Male ,Adolescent ,Experimental and Cognitive Psychology ,False memory ,050105 experimental psychology ,Developmental psychology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Arts and Humanities (miscellaneous) ,Developmental and Educational Psychology ,Humans ,0501 psychology and cognitive sciences ,Suggestion ,Memory Consolidation ,Memory errors ,Autobiographical memory ,05 social sciences ,Suggestibility ,Middle Aged ,Test (assessment) ,Mental Recall ,Female ,Memory consolidation ,Sleep (system call) ,Sleep ,Psychology ,030217 neurology & neurosurgery ,Cognitive psychology - Abstract
Sleep contributes to the consolidation of memories. This process may involve extracting the gist of learned material at the expense of details. It has thus been proposed that sleep might lead to false memory formation. Previous research examined the effect of sleep on false memory using the Deese-Roediger-McDermott (DRM) paradigm. Mixed results were found, including increases and decreases in false memory after sleep relative to wake. It has been questioned whether DRM false memories occur by the same processes as real-world false memories. Here, the effect of sleep on false memory was investigated using the Gudjonsson Suggestibility Scale. Veridical memory deteriorated after a 12-h period of wake, but not after a 12-h period including a night’s sleep. No difference in false memory was found between conditions. Although the literature supports sleep-dependent memory consolidation, the results here call into question extending this to a gist-based false memory effect.
- Published
- 2017
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26. Dopaminergic mechanisms in memory consolidation and antidepressant reversal of a chronic mild stress-induced cognitive impairment'
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Mariusz Papp, Monika Niemczyk, Ewa Litwa, Piotr Gruca, Paul Willner, Katarzyna Tota-Glowczyk, and Magdalena Lason-Tyburkiewicz
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Male ,Agonist ,medicine.drug_class ,Novel object recognition ,D1 receptors ,Prefrontal Cortex ,Hippocampus ,Nucleus accumbens ,Nucleus Accumbens ,03 medical and health sciences ,Chronic mild stress ,0302 clinical medicine ,Dopamine receptor D2 ,medicine ,Animals ,Cognitive Dysfunction ,Rats, Wistar ,D3 receptors ,Receptor ,Prefrontal cortex ,Memory Consolidation ,Original Investigation ,D2 receptors ,Pharmacology ,Depression ,Receptors, Dopamine D2 ,Receptors, Dopamine D1 ,Venlafaxine ,Risperidone ,Antidepressive Agents ,030227 psychiatry ,Dopamine Agonists ,Dopamine Antagonists ,Rat ,Antidepressant ,Memory consolidation ,Psychology ,Neuroscience ,Stress, Psychological ,030217 neurology & neurosurgery - Abstract
Cognitive deficits in depression can be modelled using the novel object recognition (NOR) test, performance in which is impaired by chronic mild stress (CMS). We aimed to examine the involvement of mesocorticolimbic DA terminal regions, and to establish the substrate for CMS-induced impairment of NOR and its reversal by chronic antidepressant treatment. In experiments 1 and 2, we examined the effect of infusions into medial PFC, dorsal hippocampus (HPC), and nucleus accumbens (NAc) shell of D1 and D2 antagonists and D3 agonist, which were predicted to impair NOR with a short (1 h) delay, and of D1 and D2 agonists and D3 antagonist, which were predicted to facilitate NOR with a long (24 h) delay. Using optimal doses identified in experiment 2, in experiments 3 and 4, we examined effects on drug-stimulated NOR of CMS and chronic treatment with venlafaxine (VFX) or risperidone (RSP). We found a wide involvement of DA systems in memory for NOR: D1 receptors in PFC, HPC, and NAc; D3 receptors in PFC and HPC; and D2 receptors in PFC. CMS impaired D2- and D3-mediated effects in PFC and HPC; antidepressants rescued those effects in PFC but not HPC. The involvement of DA in NOR is multifaceted, but the effects of CMS and antidepressants are more discrete, involving D2 and D3 receptors in PFC specifically. While raising many difficult questions, these results suggest that the D2 and D3 receptors in the medial PFC may be an important substrate for cognitive deficits in depression and their remediation. Electronic supplementary material The online version of this article (doi:10.1007/s00213-017-4651-4) contains supplementary material, which is available to authorized users.
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- 2017
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27. Intellectual disability in a prison population with anger problems in Trinidad
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Tony Bastick, John Rose, Paul Willner, and Gerard Hutchinson
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030506 rehabilitation ,Prison population ,medicine.medical_specialty ,Anger management ,medicine.medical_treatment ,media_common.quotation_subject ,Prison ,Anger ,medicine.disease ,behavioral disciplines and activities ,Mental health ,Group norms ,030227 psychiatry ,03 medical and health sciences ,Psychiatry and Mental health ,Clinical Psychology ,0302 clinical medicine ,Rating scale ,Intellectual disability ,medicine ,0305 other medical science ,Psychology ,Psychiatry ,media_common ,Clinical psychology - Abstract
This paper describes the characteristics of groups of prisoners selected to take part in an anger management programme in prisons in Trinidad. Participants completed demographic measures, an IQ assessment, mental health measures and anger rating scales. Fifty-six inmates were screened with the WASI-2 and characteristics of this group are explored in this paper. The mean IQ for the group was 72.34 and 22 had a recorded IQ below 70 (37.5%). All of the respondents reported high levels of mental health problems with their mean ratings on the SCL-90 being closer to those of inpatient psychiatric group norms than non-clinical groups. A score of less than 70 on the WASI-2 is not sufficient for a diagnosis of an Intellectual Disability. Nevertheless, the results suggest that a significant number of individuals in these prisons may have an Intellectual Disability. More research is needed to help identify these individuals and provide support.
- Published
- 2017
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28. Antidepressant, anxiolytic and procognitive effects of subacute and chronic ketamine in the chronic mild stress model of depression
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Mariusz Papp, Magdalena Lason-Tyburkiewicz, Paul Willner, and Piotr Gruca
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Male ,Imipramine ,Elevated plus maze ,Time Factors ,medicine.drug_class ,Anxiolytic ,Drug Administration Schedule ,Discrimination Learning ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Ketamine ,Rats, Wistar ,Maze Learning ,Nootropic Agents ,Pharmacology ,Dose-Response Relationship, Drug ,Depression ,business.industry ,Anhedonia ,Antidepressive Agents ,Rats ,030227 psychiatry ,Disease Models, Animal ,Psychiatry and Mental health ,Dose–response relationship ,Anti-Anxiety Agents ,Anxiogenic ,Anesthesia ,Antidepressant ,medicine.symptom ,business ,Stress, Psychological ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Ketamine is the prototype of a new generation of antidepressant drugs, which is reported in clinical studies to be effective in treatment-resistant patients, with an effect that appears within hours and lasts for a few days. Chronic mild stress (CMS) is a well-established and widely used animal model of depression, in which anhedonia, anxiogenesis and cognitive dysfunction can be observed reliably. Studies using acute or brief ketamine treatment following withdrawal from CMS have replicated the clinical finding of a rapid onset of antidepressant action. However, there have been no CMS studies of chronic daily ketamine treatment or continued stress following ketamine treatment, which would have greater translational potential in relation to the long-term maintenance of antidepressant effects. Wistar rats were drug treated following an initial 2 weeks of CMS exposure, which continued alongside daily drug treatment. A first experiment tested a range of chronic (5 weeks) ketamine doses (5-30 mg/kg); a second compared the effects of subacute (3-5 days) and chronic (5 weeks) treatment. CMS-induced anhedonic, anxiogenic and dyscognitive effects, as measured, respectively, by decreased sucrose intake, avoidance of open arms in the elevated plus maze and loss of discrimination in the novel object recognition test. A sustained antidepressant-like effect of ketamine in the sucrose intake test was observed in both experiments, with an onset at around 1 week, faster than imipramine, and an optimum dose of 10 mg/kg. Anxiogenic and dyscognitive effects of CMS, in the elevated plus maze and novel object recognition test, respectively, were fully reversed by both subacute and chronic ketamine treatment. Daily treatment with ketamine in the CMS model causes sustained long-term antidepressant, anxiolytic and procognitive effects. The demonstration of a procognitive effect of ketamine may have particular translational value.
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- 2017
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29. Effect of the COVID‐19 pandemic on the mental health of carers of people with intellectual disabilities
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Vivien Cooper, Peter E. Langdon, Biza Stenfert Kroese, Claire Clifford, Glynis H. Murphy, John Rose, Alan Watkins, Paul Willner, Hayley A Hutchings, and Steve Hiles
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Adult ,Male ,medicine.medical_specialty ,Coping (psychology) ,Pneumonia, Viral ,BF ,Computer-assisted web interviewing ,Education ,Social support ,Betacoronavirus ,Intellectual Disability ,Surveys and Questionnaires ,Intellectual disability ,Adaptation, Psychological ,medicine ,Developmental and Educational Psychology ,Humans ,Social isolation ,Psychiatry ,Child ,Pandemics ,Qualitative Research ,Health Services Needs and Demand ,SARS-CoV-2 ,Psychosocial Support Systems ,COVID-19 ,Social Support ,medicine.disease ,Mental health ,United Kingdom ,humanities ,Mental Health ,Caregivers ,Social Isolation ,Anxiety ,Female ,medicine.symptom ,Psychology ,Coronavirus Infections ,Stress, Psychological ,Qualitative research - Abstract
Introduction: \ud The measures implemented to manage the COVID‐19 pandemic have been shown to impair mental health. This problem is likely to be exacerbated for carers. Method: Informal carers (mainly parents) of children and adults with intellectual disabilities, and a comparison group of parents of children without disabilities, completed an online questionnaire. Almost all the data were collected while strict lockdown conditions were in place. Results: Relative to carers of children without intellectual disability, carers of both children and adults with intellectual disability had significantly greater levels of a wish fulfilment coping style, defeat/entrapment, anxiety, and depression. Differences were 2–3 times greater than reported in earlier pre‐pandemic studies. Positive correlations were found between objective stress scores and all mental health outcomes. Despite their greater mental health needs, carers of those with intellectual disability received less social support from a variety of sources. Conclusions: The greater mental health needs of carers in the context of lesser social support raises serious concerns. We consider the policy implications of these findings.
- Published
- 2020
30. The role of prefrontal cortex dopamine D2 and D3 receptors in the mechanism of action of venlafaxine and deep brain stimulation in animal models of treatment-responsive and treatment-resistant depression
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Magdalena Lason, Paul Willner, Piotr Gruca, Monika Niemczyk, and Mariusz Papp
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Male ,Deep brain stimulation ,Tetrahydronaphthalenes ,medicine.medical_treatment ,Deep Brain Stimulation ,Dopamine ,Prefrontal Cortex ,Venlafaxine ,Rats, Inbred WKY ,03 medical and health sciences ,Depressive Disorder, Treatment-Resistant ,0302 clinical medicine ,Dopamine receptor D2 ,Medicine ,Animals ,Pharmacology (medical) ,Rats, Wistar ,Prefrontal cortex ,Receptor ,Memory Consolidation ,Pharmacology ,Behavior, Animal ,business.industry ,Depression ,Receptors, Dopamine D2 ,Receptors, Dopamine D3 ,Venlafaxine Hydrochloride ,medicine.disease ,030227 psychiatry ,Rats ,Psychiatry and Mental health ,Mechanism of action ,Dopamine receptor ,Dopamine Agonists ,Models, Animal ,Dopamine Antagonists ,medicine.symptom ,business ,Neuroscience ,Treatment-resistant depression ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Aims: The Wistar-Kyoto rat has been validated as an animal model of treatment-resistant depression. Here we investigated a role of dopamine D2 and D3 receptors in the ventro-medial prefrontal cortex in the mechanism of action of deep brain stimulation in Wistar-Kyoto rats and venlafaxine in Wistar rats. Methods: Wistar or Wistar-Kyoto rats were exposed chronically to chronic mild stress. Wistar rats were treated chronically with venlafaxine (10 mg/kg) beginning after two weeks of chronic mild stress; Wistar-Kyoto rats received two sessions of deep brain stimulation before behavioural tests. L-742,626 (1 µg), a D2 receptor agonist, or 7-OH DPAT (3 µg), a D3 receptor antagonist, were infused into the ventro-medial prefrontal cortex immediately following the exposure trial in the Novel Object Recognition Test, and discrimination between novel and familiar object was tested one hour later. Results: Chronic mild stress decreased sucrose intake and impaired memory consolidation; these effects were reversed by venlafaxine in Wistar rats and deep brain stimulation in Wistar-Kyoto rats. In control animals, L-742,626 and 7-OH DPAT also impaired memory consolidation. In Wistar rats, venlafaxine reversed the effect of L-742,626 in controls, but not in the chronic mild stress group, and venlafaxine did not reverse the effect of 7-OH DPAT in either group. In Wistar-Kyoto rats, deep brain stimulation reversed the effect of both L-742,626 and 7-OH DPAT in both control and chronic mild stress groups. Conclusions: We conclude that the action of venlafaxine to reverse the impairment of memory consolidation caused by chronic mild stress in Wistar rats involves D2 receptors in the ventro-medial prefrontal cortex; but the effect of deep brain stimulation to reverse the same effect in Wistar-Kyoto rats does not.
- Published
- 2019
31. Announcement: Change of Editor
- Author
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Louk J. M. J. Vanderschuren and Paul Willner
- Subjects
Pharmacology ,World Wide Web ,Psychiatry and Mental health ,Text mining ,History ,business.industry ,business - Published
- 2021
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32. CBT in a Caribbean Context: A Controlled Trial of Anger Management in Trinidadian Prisons
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Paul Willner, Tony Bastick, John Rose, Gerard Hutchinson, and Ian Burke
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Adult ,Male ,050103 clinical psychology ,Anger management ,genetic structures ,media_common.quotation_subject ,medicine.medical_treatment ,Psychological intervention ,Context (language use) ,Prison ,Anger ,behavioral disciplines and activities ,law.invention ,Randomized controlled trial ,law ,Intervention (counseling) ,Adaptation, Psychological ,mental disorders ,medicine ,Humans ,0501 psychology and cognitive sciences ,media_common ,Cognitive Behavioral Therapy ,Prisoners ,05 social sciences ,General Medicine ,Middle Aged ,Group Processes ,Clinical trial ,Clinical Psychology ,Trinidad and Tobago ,nervous system ,Anger Management Therapy ,Female ,Psychology ,psychological phenomena and processes ,050104 developmental & child psychology ,Clinical psychology - Abstract
Background: Anger causes significant problems in offenders and to date few interventions have been described in the Caribbean region. Aim: To evaluate a package of CBT-based Anger Management Training provided to offenders in prison in Trinidad. Method: A controlled clinical trial with 85 participants who participated in a 12-week prison-based group anger management programme, of whom 57 (67%: 16 control, 41 intervention) provided pretrial and posttrial outcome data at Times 1 and 2. Results: Intervention and control groups were not directly comparable so outcome was analysed using t-tests. Reductions were noted for state and trait anger and anger expression, with an increase in coping skills for the intervention group. No changes were noted in the control group. The improvements seen on intervention were maintained at 4 month follow-up for a sub-group of participants for whom data were available. Several predictors of outcomes were identified.
- Published
- 2016
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33. Trauma-focussed cognitive-behaviour therapy for people with mild intellectual disabilities: outcomes of a pilot study
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Sara Willott, Paul Willner, Frances Taylor, Philippa Smith, Ruth Graham, Andrew Stott, Biza Stenfert Kroese, and Tara Rutter
- Subjects
030506 rehabilitation ,medicine.medical_specialty ,Interpretative phenomenological analysis ,Complex post-traumatic stress disorder ,media_common.quotation_subject ,05 social sciences ,Nice ,medicine.disease ,Mental health ,Clinical trial ,03 medical and health sciences ,Psychiatry and Mental health ,Feeling ,Intervention (counseling) ,Intellectual disability ,medicine ,0501 psychology and cognitive sciences ,0305 other medical science ,Psychiatry ,Psychology ,computer ,050104 developmental & child psychology ,computer.programming_language ,media_common ,Clinical psychology - Abstract
Purpose Trauma-focussed cognitive-behaviour therapy (TF-CBT) is the most effective treatment for post-traumatic stress disorder (PTSD). Individuals who present with complex PTSD are among the most complex and challenging patients seen by intellectual disability psychology and psychiatry services. The purpose of this paper is to study TF-CBT intervention for people with intellectual disabilities and complex PTSD. Design/methodology/approach Three groups of adults with intellectual disabilities (ID) presenting with complex PTSD (n=3, n=5 and n=4) were treated using a 12-week manualised intervention adapted from a procedure routinely used in adult mental health services. Participants completed the Impact of Event Scale as adapted for people with intellectual disabilities (IES-ID) before and after the intervention, and interviews conducted to ascertain their experiences of the group were analysed using interpretative phenomenological analysis (IPA). Findings The ten participants who completed the intervention showed a 27 per cent decrease in median Impact of Event Scale Intellectual Disabilities scores, equivalent to a medium effect size (d=0.50). Five themes were identified from the interviews: being listened to; it is nice to know you are not the only one; being in a group can be stressful; the importance of feeling safe; achieving and maintaining change. Participants also provided constructive feedback to promote improvements to the manual. Research limitations/implications A feasibility study followed by methodologically robust clinical trials is now needed to establish the effectiveness of the intervention and its utility in clinical practice. Practical implications This small study has confirmed the potential of TF-CBT as an intervention for extremely vulnerable individuals with ID who present with complex PTSD. Social implications The findings indicate that a group intervention is both feasible for and acceptable to adults with ID. Originality/value To date, no study has investigated the effectiveness and feasibility of a TF-CBT group intervention for adults with mild ID.
- Published
- 2016
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34. The UK Mental Capacity Act and consent to research participation: asking the right question
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Paul Willner
- Subjects
Health (social science) ,Research Subjects ,050801 communication & media studies ,Affect (psychology) ,Ethics, Research ,03 medical and health sciences ,0508 media and communications ,0302 clinical medicine ,Arts and Humanities (miscellaneous) ,Mental capacity ,Humans ,Mental Competency ,Meaning (existential) ,Relation (history of concept) ,Research ethics ,Informed Consent ,030214 geriatrics ,business.industry ,Research ,Health Policy ,05 social sciences ,Critical question ,Public relations ,United Kingdom ,Issues, ethics and legal aspects ,Privacy ,business ,Psychology ,Social psychology ,Personally identifiable information ,Confidentiality ,Ethical Analysis - Abstract
This paper considers the meaning of the term ‘intrusive research’, as used in the UK Mental Capacity Act 2005 (MCA), in relation to studies in which an informant is asked to provide information about or on behalf of a person who lacks capacity to consent, and who is not otherwise involved in the study. The MCA defines ‘intrusive research’ as research that would legally require consent if it involved people with capacity. The relevant ethical principles are that consent should be sought from people who would be affected by a piece of research and that this requirement should be implemented proportionately. The critical question, for investigators and research ethics committees, is: would provision of the personal information specified in the research protocol significantly affect a person whose capacity is not impaired? If the answer to this question is ‘no’, then the study falls outside the definition of ‘intrusive research’, and the MCA does not apply.
- Published
- 2017
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35. Announcement of Special Issues for 2019: Stress and neuroinflammation
- Author
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Paul, Willner, primary, Louk, Vanderschuren, additional, Bart, Ellenbroek, additional, and Paul, Willner, additional
- Published
- 2018
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36. Validation of chronic mild stress in the Wistar-Kyoto rat as an animal model of treatment-resistant depression
- Author
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Katarzyna Tota-Glowczyk, Monika Niemczyk, Piotr Gruca, Paul Willner, Ewa Litwa, Mariusz Papp, and Magdalena Lason
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Male ,Elevated plus maze ,Imipramine ,Deep brain stimulation ,medicine.medical_treatment ,Prefrontal Cortex ,Citalopram ,Pharmacology ,Rats, Inbred WKY ,03 medical and health sciences ,Depressive Disorder, Treatment-Resistant ,0302 clinical medicine ,medicine ,Animals ,Ketamine ,Rats, Wistar ,Depressive Disorder ,Behavior, Animal ,business.industry ,Depression ,Venlafaxine Hydrochloride ,medicine.disease ,Antidepressive Agents ,030227 psychiatry ,Rats ,Psychiatry and Mental health ,Disease Models, Animal ,Anxiogenic ,Antidepressant ,business ,Treatment-resistant depression ,030217 neurology & neurosurgery ,Stress, Psychological ,medicine.drug - Abstract
A recent review proposed four criteria for an animal model of treatment-resistant depression (TRD): a phenotypic resemblance to a risk factor for depression; enhanced response to stress; nonresponse to antidepressant drugs and response to treatments effective in TRD, such as deep brain stimulation (DBS) of the prefrontal cortex or ketamine. Chronic mild stress (CMS) provides a valid model of depression; the Wistar-Kyoto (WKY) rat is considered to be nonresponsive to antidepressant drugs. Here, we applied CMS to WKY rats. WKY and Wistar rats were exposed to CMS, then treated with saline, imipramine, citalopram or venlafaxine. After 5 weeks of CMS and 3 weeks of drug treatment, all WKY groups were implanted unilaterally with DBS electrodes in the prefrontal cortex, and examined in sucrose intake, elevated plus maze (EPM; decreased entries and time in the open arms) and novel object recognition (decreased exploration) tests, following 2×2 h of DBS. CMS decreased sucrose intake, open arm entries on the EPM, and object recognition. Relative to Wistars, WKY rats showed evidence of increased emotionality in the EPM and novel object recognition tests, and a greater impact of CMS on body weight gain and open arm entries. Wistars responded to drug treatment with an increase in sucrose intake but WKY were nonresponsive to drug treatment on all three behavioural tests. With one exception, DBS reversed the anhedonic, anxiogenic and dyscognitive effects of CMS in all groups of WKY rats. In a further experiment, subacute ketamine (10 mg/kg) also normalized behaviour on all three tests. We conclude that WKY rats subjected to CMS meet all four criteria for a valid model of TRD, and provide a basis for studying the mechanism of action of DBS.
- Published
- 2018
37. Behavioural pharmacology and brain-body signalling processes
- Author
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Paul Willner, Jack Bergman, Louk J. M. J. Vanderschuren, and Bart A. Ellenbroek
- Subjects
Pharmacology ,Psychiatry and Mental health ,Behavioural pharmacology ,Behavior ,Signalling ,Taverne ,Animals ,Brain ,Humans ,Biology ,Neuroscience ,Gastrointestinal Microbiome - Published
- 2018
38. Cognitive-behavioural therapy for heroin and cocaine use: Ecological momentary assessment of homework simplification and compliance
- Author
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Paul Willner, Kenzie L. Preston, Karran A. Phillips, Damiya Whitaker, Jessica Willner-Reid, Amber R. Pulaski, and David H. Epstein
- Subjects
Adult ,Male ,050103 clinical psychology ,Methadone maintenance ,Psychotherapist ,Adolescent ,Ecological Momentary Assessment ,medicine.medical_treatment ,media_common.quotation_subject ,education ,Psychological intervention ,Craving ,Affect (psychology) ,Article ,Cocaine-Related Disorders ,Young Adult ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,Arts and Humanities (miscellaneous) ,Intervention (counseling) ,Task Performance and Analysis ,mental disorders ,Developmental and Educational Psychology ,medicine ,Humans ,0501 psychology and cognitive sciences ,media_common ,Cognitive Behavioral Therapy ,Heroin Dependence ,Ecology ,Addiction ,05 social sciences ,Environmental exposure ,Middle Aged ,United States ,030227 psychiatry ,Affect ,Psychiatry and Mental health ,Clinical Psychology ,Logistic Models ,Linear Models ,Cognitive therapy ,Female ,medicine.symptom ,Psychology ,human activities ,Methadone ,Clinical psychology - Abstract
Objectives The purpose of this study was to evaluate the effects of homework-task difficulty and electronic-diary reminders on written homework completion during cognitive-behavioural therapy (CBT) for addiction. Completion of homework is an important element in CBT that may affect outcome. Design All participants received all combinations of our two interventions in a factorial 2 × 2 counterbalanced Latin-square design. Methods Methadone-maintained cocaine and heroin users were given homework between each of 12 weekly CBT sessions and carried electronic diaries that collected ecological momentary assessment (EMA) data on craving and exposure to drug-use triggers in four 3-week blocks assessing two levels of homework difficulty and prompted and unprompted homework. Results Neither simplified (picture-based) homework nor electronic reminders increased homework completion. In EMA reports, standard but not simplified homework seemed to buffer the craving that followed environmental exposure to drug cues. EMA recordings before and after the CBT intervention confirmed a decrease over time in craving for cocaine and heroin. Conclusions These findings demonstrate the utility of EMA to assess treatment effects. However, the hypothesis that simplified homework would increase compliance was not supported. Practitioner points Our simplifications of homework assignments for cognitive-behavioural therapy were mostly ineffective, or even counterproductive, perhaps because they did not engage sufficient depth of processing or because they were perceived as too simplistic. Our reminder beeps for homework were mostly ineffective, or even counterproductive, suggesting that mobile electronic interventions for substance-use disorders may need to be more interactive.
- Published
- 2015
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39. Managers’ views of the effects on their service of hosting a cognitive-behavioural anger management group
- Author
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P MacMahon, Paul Willner, David John Felce, John Rose, Nicola Rose, A Stimpson, Julia Townson, Kerenza Hood, Biza Stenfert Kroese, and Andrew Jahoda
- Subjects
Service (business) ,Anger management ,business.industry ,medicine.medical_treatment ,Applied psychology ,Professional development ,medicine.disease ,Group psychotherapy ,Psychiatry and Mental health ,Intervention (counseling) ,Intellectual disability ,Medicine ,Thematic analysis ,business ,Clinical psychology ,Qualitative research - Abstract
Purpose – The purpose of this paper is to investigate how service managers perceive their service prior to, and following the delivery of a cognitive-behavioural therapy (CBT) anger management group for individuals with an intellectual disability. Design/methodology/approach – Telephone interviews were conducted with seven service managers, before and after a CBT group intervention. The interviews were recorded, transcribed and analysed using thematic analysis to identify common and/or contrasting themes. Findings – Before the intervention took place managers observed a lack of consistency in how their staff dealt with challenging incidents and the serious consequences these incidents had for service users as well as staff. They spoke about the importance of multi-disciplinary working and good quality staff selection, support and training. After the group intervention managers commented on a positive “spilling-out effect” whereby the whole organisation was influenced by the intervention, a greater willingness on the part of service users to talk about their problems, and an increased confidence in the staff members who had co-facilitated the group work. Research limitations/implications – The implications of the themes raised are discussed and recommendations for further research are suggested. Originality/value – This research provides a unique contribution of managers’ views and insight into how hosting a CBT group intervention impacted on their wider services.
- Published
- 2015
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40. The behavioural pharmacology of dementia
- Author
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Gernot Riedel, Jack Bergman, Bart A. Ellenbroek, Paul Willner, and Louk J. M. J. Vanderschuren
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0301 basic medicine ,Pharmacology ,Behavioural pharmacology ,medicine.medical_specialty ,business.industry ,medicine.disease ,03 medical and health sciences ,Psychiatry and Mental health ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,medicine ,Dementia ,Animals ,Humans ,Psychiatry ,business ,Nootropic Agents - Published
- 2017
41. Antidepressant efficacy of deep brain stimulation in Wistar Kyoto rats exposed to chronic mild stress: Animal model of treatment-resistant depression
- Author
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Paul Willner, Magdalena Lason-Tyburkiewicz, M. Niemczyk, Mariusz Papp, K. Tota-Glowczyk, Ewa Litwa, and Piotr Gruca
- Subjects
Pharmacology ,Antidepressant efficacy ,Deep brain stimulation ,business.industry ,medicine.medical_treatment ,medicine.disease ,Psychiatry and Mental health ,Animal model ,Neurology ,Mild stress ,Medicine ,Pharmacology (medical) ,Neurology (clinical) ,Wistar Kyoto Rats ,business ,Treatment-resistant depression ,Biological Psychiatry - Published
- 2019
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42. The behavioural pharmacology of opioids
- Author
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Paul Willner, Jack Bergman, and Louk J. M. J. Vanderschuren
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Pharmacology ,Behavioural pharmacology ,Psychotherapist ,business.industry ,MEDLINE ,Pain ,Opioid-Related Disorders ,Analgesics, Opioid ,Behavioral Medicine ,Psychiatry and Mental health ,Taverne ,Humans ,Medicine ,Pain psychology ,business - Published
- 2020
43. ‘It's made all of us bond since that course…’ - a qualitative study of service users' experiences of a CBT anger management group intervention
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Julia Townson, Paul Willner, Kerenza Hood, N Rose, A Stimpson, B Stenfert Kroese, Andrew Jahoda, John Rose, and P MacMahon
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Psychotherapist ,Anger management ,Interpretative phenomenological analysis ,medicine.medical_treatment ,media_common.quotation_subject ,Rehabilitation ,Context (language use) ,Anger ,law.invention ,Psychiatry and Mental health ,Neurology ,Arts and Humanities (miscellaneous) ,Randomized controlled trial ,law ,Intervention (counseling) ,medicine ,Neurology (clinical) ,Group work ,Psychology ,Clinical psychology ,Qualitative research ,media_common - Abstract
Background People with intellectual disabilities (ID) are rarely asked about their experiences as users of psychological services and little is known about the views of clients with ID who have undergone cognitive behavioural therapy (CBT). This study aimed to gather the views of adults with ID who had recently taken part in a cluster randomised control trial (RCT) of a staff-delivered manualised CBT anger management group intervention. Method A qualitative method, Interpretative Phenomenological Analysis (IPA), was employed and eleven participants were interviewed. The interviews took place after the intervention, within two weeks of the end of the group, to gain an understanding of service users' experiences of participating in a CBT group. Results IPA of the interview transcripts indicated that the intervention was experienced as effective and enjoyable and a number of themes were identified including: ‘the importance of relationships’, ‘a new me’, ‘new and improved relationships’, ‘presenting myself in a positive light’ and ‘what the group didn't change’. Conclusions The results will be discussed in the context of applying group CBT for adults with ID and implications for service development.
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- 2014
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44. Behavioural aspects of neuroinflammation
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Paul Willner, Jack Bergman, and Louk J. M. J. Vanderschuren
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Pharmacology ,Inflammation ,Psychiatry and Mental health ,Behavior ,Neuroimmunomodulation ,Taverne ,Animals ,Brain ,Humans ,Psychology ,Neuroscience ,Neuroinflammation - Published
- 2019
- Full Text
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45. Announcement of special issue: translational research in behavioural pharmacology
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Bart A. Ellenbroek, Jack Bergman, Paul Willner, and Louk J. M. J. Vanderschuren
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Pharmacology ,Cognitive science ,Psychiatry and Mental health ,Behavioural pharmacology ,Translational research ,Psychology - Published
- 2019
- Full Text
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46. Announcement of special issue for 2020: The behavioural pharmacology of opioids
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Louk J. M. J. Vanderschuren, Bart A. Ellenbroek, Jack Bergman, and Paul Willner
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Pharmacology ,Psychiatry and Mental health - Published
- 2019
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47. The neurobiology of aggression: implications for the pharmacotherapy of aggressive challenging behaviour by people with intellectual disabilities
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Paul Willner
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education.field_of_study ,Psychotherapist ,Risperidone ,Challenging behaviour ,Aggression ,Rehabilitation ,Population ,Poison control ,Context (language use) ,medicine.disease ,Psychiatry and Mental health ,Pharmacotherapy ,Neurology ,Arts and Humanities (miscellaneous) ,Intellectual disability ,medicine ,Neurology (clinical) ,medicine.symptom ,education ,Psychology ,Neuroscience ,Clinical psychology ,medicine.drug - Abstract
Aim The aim of this review is to summarise current understanding of the neurobiology of aggression and within this context to consider the evidence base for the pharmacotherapy of aggressive challenging behaviour by people with intellectual disabilities (ID). Evidence Aggressive encounters involve a variety of psychological processes and progress has been made in understanding the brain mechanisms involved. However, the role in aggression of the neurotransmitters serotonin, dopamine and γ-aminobutyric acid is no longer as clear as it once appeared, with the result that predictions cannot be made with confidence about drug effects on aggression. There have been relatively few controlled trials of pharmacotherapy for aggression in people with ID, or, indeed, in the general population, and their outcomes have largely been negative. Conclusion With the possible exception of risperidone, there is no reliable evidence that antidepressant, neuroleptic or anticonvulsant drugs are effective treatments for aggression by people with ID.
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- 2014
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48. Cognitive behavioural anger management intervention for people with intellectual disabilities: costs of intervention and impact on health and social care resource use
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C Lammie, P MacMahon, J Shead, Paul Willner, Kerenza Hood, David John Felce, Deborah Cohen, Jacqui Nuttall, Biza Stenfert Kroese, C Woodgate, David Gillespie, John Rose, A Stimpson, Andrew Jahoda, Julia Townson, and N Rose
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medicine.medical_specialty ,Anger management ,Aggression ,media_common.quotation_subject ,medicine.medical_treatment ,Rehabilitation ,Anger ,medicine.disease ,law.invention ,Psychiatry and Mental health ,Neurology ,Arts and Humanities (miscellaneous) ,Randomized controlled trial ,law ,Intervention (counseling) ,Intellectual disability ,medicine ,Cognitive therapy ,Neurology (clinical) ,medicine.symptom ,Psychiatry ,Baseline (configuration management) ,Psychology ,health care economics and organizations ,media_common - Abstract
Background Anger and aggression among adults with intellectual disability (ID) are associated with a range of adverse consequences for their well-being and that of their family or staff carers. The aims were to evaluate the effectiveness of an anger management intervention for adults with mild to moderate ID and to evaluate the costs of the intervention and its impact on health and social care resource use. This paper is concerned with the latter aim. Methods A cluster-randomised controlled trial was conducted involving day services for adults with ID in Scotland, England and Wales. Incremental costs of delivering the intervention and its impact on subsequent total health and social care package costs were calculated. Full data comparing costs between baseline and follow-up 10 months later were collected for 67 participants in the intervention arm and 62 participants in the control arm. Cost differences between the groups at follow-up, adjusted for baseline levels, were calculated using non-parametric bootstrapping controlling for clustering. Results The mean hourly excess cost of intervention over treatment as usual was £12.34. A mean adjusted cost difference of £22.46 per person per week in favour of the intervention group was found but this was not statistically significant. Conclusions The baseline-adjusted cost difference at follow-up would result in a fairly immediate compensation for the excess costs of intervention, provided the difference is not a statistical artefact. Further research is needed to clarify the extent to which it might represent a real saving in service support costs.
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- 2014
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49. Development of a scale to measure fidelity to manualized group-based cognitive behavioural interventions for people with intellectual disabilities
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C Lammie, J Shead, David Gillespie, Paul Willner, David John Felce, Julia Townson, Kerenza Hood, N Rose, Jacqueline Nuttall, C Woodgate, A Stimpson, John Rose, P MacMahon, Andrew Jahoda, and Biza Stenfert Kroese
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Adult ,media_common.quotation_subject ,medicine.medical_treatment ,Fidelity ,Context (language use) ,Anger ,behavioral disciplines and activities ,law.invention ,Clinical Protocols ,Randomized controlled trial ,law ,Intellectual Disability ,Intervention (counseling) ,Intellectual disability ,Developmental and Educational Psychology ,medicine ,Humans ,media_common ,Cognitive Behavioral Therapy ,medicine.disease ,Checklist ,Clinical Psychology ,Treatment Outcome ,Scale (social sciences) ,Psychotherapy, Group ,Cognitive therapy ,Guideline Adherence ,Psychology ,Clinical psychology - Abstract
The context for the present study was a cluster-randomized controlled trial of a group-based anger-management intervention, delivered by day-service staff. We aimed to develop a scale to measure the fidelity of manualized cognitive-behavioural therapy (CBT) delivered to adults with intellectual disabilities in group-based settings. A 30-item monitoring instrument (the MAnualized Group Intervention Check: MAGIC) was adapted from an existing fidelity-monitor instrument for individual CBT. Two sessions for 27 groups were observed by pairs of monitors who had no other contact with the intervention. 16 observers participated, in 15 unique pairings. Observers recorded high levels of inter-rater reliability and the scale had good internal consistency. Fidelity ratings predicted two key outcomes of the intervention, and were themselves predicted by the therapists' clinical supervisors.
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- 2013
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50. Group-based cognitive–behavioural anger management for people with mild to moderate intellectual disabilities: cluster randomised controlled trial
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Paul Willner, P MacMahon, Jacqueline Nuttall, C Woodgate, C Lammie, Nicola Rose, A Stimpson, Julia Townson, Kerenza Hood, David Gillespie, David Cohen, John Rose, David John Felce, J Shead, Biza Stenfert Kroese, and Andrew Jahoda
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Adult ,Male ,050103 clinical psychology ,medicine.medical_specialty ,Anger management ,Challenging behaviour ,media_common.quotation_subject ,medicine.medical_treatment ,Poison control ,Anger ,Suicide prevention ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Intellectual Disability ,Intervention (counseling) ,Adaptation, Psychological ,medicine ,Cluster Analysis ,Humans ,0501 psychology and cognitive sciences ,030212 general & internal medicine ,Cluster randomised controlled trial ,Psychiatry ,media_common ,Cognitive Behavioral Therapy ,05 social sciences ,Middle Aged ,Psychiatry and Mental health ,Treatment Outcome ,Costs and Cost Analysis ,Psychotherapy, Group ,Female ,Psychology ,Clinical psychology - Abstract
BackgroundMany people with intellectual disabilities find it hard to control their anger and this often leads to aggression which can have serious consequences, such as exclusion from mainstream services and the need for potentially more expensive emergency placements.AimsTo evaluate the effectiveness of a cognitive–behavioural therapy (CBT) intervention for anger management in people with intellectual disabilities.MethodA cluster-randomised trial of group-based 12-week CBT, which took place in day services for people with intellectual disabilities and was delivered by care staff using a treatment manual. Participants were 179 service users identified as having problems with anger control randomly assigned to either anger management or treatment as usual. Assessments were conducted before the intervention, and at 16 weeks and 10 months after randomisation (trial registration: ISRCTN37509773).ResultsThe intervention had only a small, and non-significant, effect on participants' reports of anger on the Provocation Index, the primary outcome measure (mean difference 2.8, 95% Cl −1.7 to 7.4 at 10 months). However, keyworker Provocation Index ratings were significantly lower in both follow-up assessments, as were service-user ratings on another self-report anger measure based on personally salient triggers. Both service users and their keyworkers reported greater usage of anger coping skills at both follow-up assessments and keyworkers and home carers reported lower levels of challenging behaviour.ConclusionsThe intervention was effective in improving anger control by people with intellectual disabilities. It provides evidence of the effectiveness of a CBT intervention for this client group and demonstrates that the staff who work with them can be trained and supervised to deliver such an intervention with reasonable fidelity.
- Published
- 2013
- Full Text
- View/download PDF
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