Identifying health inequalities in individuals with major mental illness (MMI) using routine data

Abstract and Summary of Thesis: Background: Individuals with Major Mental Illness (such as schizophrenia and bipolar disorder) experience increased rates of physical health comorbidity compared to the general population. They also experience inequalities in access to certain aspects of healthcare. This ultimately leads to premature mortality. Studies detailing patterns of physical health comorbidity are limited by their definitions of comorbidity, single disease approach to comorbidity and by the study of heterogeneous groups. To date the investigation of possible sources of healthcare inequalities experienced by individuals with Major Mental Illness (MMI) is relatively limited. Moreover studies detailing the extent of premature mortality experienced by individuals with MMI vary both in terms of the measure of premature mortality reported and age of the cohort investigated, limiting their generalisability to the wider population. Therefore local and national data can be used to describe patterns of physical health comorbidity, investigate possible reasons for health inequalities and describe mortality rates. These findings will extend existing work in this area. Aims and Objectives: To review the relevant literature regarding: patterns of physical health comorbidity, evidence for inequalities in physical healthcare and evidence for premature mortality for individuals with MMI. To examine the rates of physical health comorbidity in a large primary care database and to assess for evidence for inequalities in access to healthcare using both routine primary care prescribing data and incentivised national Quality and Outcome Framework (QOF) data. Finally to examine the rates of premature mortality in a local context with a particular focus on cause of death across the lifespan and effect of International Classification of Disease Version 10 (ICD 10) diagnosis and socioeconomic status on rates and cause of death. Methods: A narrative review of the literature surrounding patterns of physical health comorbidity, the evidence for inequalities in physical healthcare and premature mortality in MMI was undertaken. Rates of physical health comorbidity and multimorbidity in schizophrenia and bipolar disorder were examined using a large primary care dataset (Scottish Programme for Improving Clinical Effectiveness in Primary Care (SPICE)). Possible inequalities in access to healthcare were investigated by comparing patterns of prescribing in individuals with MMI and comorbid physical health conditions with prescribing rates in individuals with physical health conditions without MMI using SPICE data. Potential inequalities in access to health promotion advice (in the form of smoking cessation) and prescribing of Nicotine Replacement Therapy (NRT) were also investigated using SPICE data. Possible inequalities in access to incentivised primary healthcare were investigated using National Quality and Outcome Framework (QOF) data. Finally a pre-existing case register (Glasgow Psychosis Clinical Information System (PsyCIS)) was linked to Scottish Mortality data (available from the Scottish Government Website) to investigate rates and primary cause of death in individuals with MMI. Rate and primary cause of death were compared to the local population and impact of age, socioeconomic status and ICD 10 diagnosis (schizophrenia vs. bipolar disorder) were investigated. Results: Analysis of the SPICE data found that sixteen out of the thirty two common physical comorbidities assessed, occurred significantly more frequently in individuals with schizophrenia. In individuals with bipolar disorder fourteen occurred more frequently. The most prevalent chronic physical health conditions in individuals with schizophrenia and bipolar disorder were: viral hepatitis (Odds Ratios (OR) 3.99 95% Confidence Interval (CI) 2.82-5.64 and OR 5.90 95% CI 3.16-11.03 respectively), constipation (OR 3.24 95% CI 3.01-3.49 and OR 2.84 95% CI 2.47-3.26 respectively) and Parkinson’s disease (OR 3.07 95% CI 2.43-3.89 and OR 2.52 95% CI 1.60-3.97 respectively). Both groups had significantly increased rates of multimorbidity compared to controls: in the schizophrenia group OR for two comorbidities was 1.37 95% CI 1.29-1.45 and in the bipolar disorder group OR was 1.34 95% CI 1.20-1.49. In the studies investigating inequalities in access to healthcare there was evidence of: under-recording of cardiovascular-related conditions for example in individuals with schizophrenia: OR for Atrial Fibrillation (AF) was 0.62 95% CI 0.52 - 0.73, for hypertension 0.71 95% CI 0.67 - 0.76, for Coronary Heart Disease (CHD) 0.76 95% CI 0.69 - 0.83 and for peripheral vascular disease (PVD) 0.83 95% CI 0.72 - 0.97. Similarly in individuals with bipolar disorder OR for AF was 0.56 95% CI 0.41-0.78, for hypertension 0.69 95% CI 0.62 - 0.77 and for CHD 0.77 95% CI 0.66 - 0.91. There was also evidence of less intensive prescribing for individuals with schizophrenia and bipolar disorder who had comorbid hypertension and CHD compared to individuals with hypertension and CHD who did not have schizophrenia or bipolar disorder. Rate of prescribing of statins for individuals with schizophrenia and CHD occurred significantly less frequently than in individuals with CHD without MMI (OR 0.67 95% CI 0.56-0.80). Rates of prescribing of 2 or more anti-hypertensives were lower in individuals with CHD and schizophrenia and CHD and bipolar disorder compared to individuals with CHD without MMI (OR 0.66 95% CI 0.56-0.78 and OR 0.55 95% CI 0.46-0.67, respectively). Smoking was more common in individuals with MMI compared to individuals without MMI (OR 2.53 95% CI 2.44-2.63) and was particularly increased in men (OR 2.83 95% CI 2.68-2.98). Rates of ex-smoking and non-smoking were lower in individuals with MMI (OR 0.79 95% CI 0.75-0.83 and OR 0.50 95% CI 0.48-0.52 respectively). However recorded rates of smoking cessation advice in smokers with MMI were significantly lower than the recorded rates of smoking cessation advice in smokers with diabetes (88.7% vs. 98.0%, p<0.001), smokers with CHD (88.9% vs. 98.7%, p<0.001) and smokers with hypertension (88.3% vs. 98.5%, p<0.001) without MMI. The odds ratio of NRT prescription was also significantly lower in smokers with MMI without diabetes compared to smokers with diabetes without MMI (OR 0.75 95% CI 0.69-0.81). Similar findings were found for smokers with MMI without CHD compared to smokers with CHD without MMI (OR 0.34 95% CI 0.31-0.38) and smokers with MMI without hypertension compared to smokers with hypertension without MMI (OR 0.71 95% CI 0.66-0.76). At a national level, payment and population achievement rates for the recording of body mass index (BMI) in MMI was significantly lower than the payment and population achievement rates for BMI recording in diabetes throughout the whole of the UK combined: payment rate 92.7% (Inter Quartile Range (IQR) 89.3-95.8 vs. 95.5% IQR 93.3-97.2, p<0.001 and population achievement rate 84.0% IQR 76.3-90.0 vs. 92.5% IQR 89.7-94.9, p<0.001 and for each country individually: for example in Scotland payment rate was 94.0% IQR 91.4-97.2 vs. 96.3% IQR 94.3-97.8, p<0.001. Exception rate was significantly higher for the recording of BMI in MMI than the exception rate for BMI recording in diabetes for the UK combined: 7.4% IQR 3.3-15.9 vs. 2.3% IQR 0.9-4.7, p<0.001 and for each country individually. For example in Scotland exception rate in MMI was 11.8% IQR 5.4-19.3 compared to 3.5% IQR 1.9-6.1 in diabetes. Similar findings were found for Blood Pressure (BP) recording: across the whole of the UK payment and population achievement rates for BP recording in MMI were also significantly reduced compared to payment and population achievement rates for the recording of BP in chronic kidney disease (CKD): payment rate: 94.1% IQR 90.9-97.1 vs.97.8% IQR 96.3-98.9 and p<0.001 and population achievement rate 87.0% IQR 81.3-91.7 vs. 97.1% IQR 95.5-98.4, p<0.001. Exception rates again were significantly higher for the recording of BP in MMI compared to CKD (6.4% IQR 3.0-13.1 vs. 0.3% IQR 0.0-1.0, p<0.001). There was also evidence of differences in rates of recording of BMI and BP in MMI across the UK. BMI and BP recording in MMI were significantly lower in Scotland compared to England (BMI:-1.5% 99% CI -2.7 to -0.3%, p<0.001 and BP: -1.8% 99% CI -2.7 to -0.9%, p<0.001). While rates of BMI and BP recording in diabetes and CKD were similar in Scotland compared to England (BMI: -0.5 99% CI -1.0 to 0.05, p=0.004 and BP: 0.02 99% CI -0.2 to 0.3, p=0.797). Data from the PsyCIS cohort showed an increase in Standardised Mortality Ratios (SMR) across the lifespan for individuals with MMI compared to the local Glasgow and wider Scottish populations (Glasgow SMR 1.8 95% CI 1.6-2.0 and Scotland SMR 2.7 95% CI 2.4-3.1). Increasing socioeconomic deprivation was associated with an increased overall rate of death in MMI (350.3 deaths/10,000 population/5 years in the least deprived quintile compared to 794.6 deaths/10,000 population/5 years in the most deprived quintile). No significant difference in rate of death for individuals with schizophrenia compared with bipolar disorder was reported (6.3% vs. 4.9%, p=0.086), but primary cause of death varied: with higher rates of suicide in individuals with bipolar disorder (22.4% vs. 11.7%, p=0.04). Discussion: Local and national datasets can be used for epidemiological study to inform local practice and complement existing national and international studies. While the strengths of this thesis include the large data sets used and therefore their likely representativeness to the wider population, some limitations largely associated with using secondary data sources are acknowledged. While this thesis has confirmed evidence of increased physical health comorbidity and multimorbidity in individuals with MMI, it is likely that these findings represent a significant under reporting and likely under recognition of physical health comorbidity in this population. This is likely due to a combination of patient, health professional and healthcare system factors and requires further investigation. Moreover, evidence of inequality in access to healthcare in terms of: physical health promotion (namely smoking cessation advice), recording of physical health indices (BMI and BP), prescribing of medications for the treatment of physical illness and prescribing of NRT has been found at a national level. While significant premature mortality in individuals with MMI within a Scottish setting has been confirmed, more work is required to further detail and investigate the impact of socioeconomic deprivation on cause and rate of death in this population. It is clear that further education and training is required for all healthcare staff to improve the recognition, diagnosis and treatment of physical health problems in this population with the aim of addressing the significant premature mortality that is seen. Conclusions: Future work lies in the challenge of designing strategies to reduce health inequalities and narrow the gap in premature mortality reported in individuals with MMI. Models of care that allow a much more integrated approach to diagnosing, monitoring and treating both the physical and mental health of individuals with MMI, particularly in areas of social and economic deprivation may be helpful. Strategies to engage this “hard to reach” population also need to be developed. While greater integration of psychiatric services with primary care and with specialist medical services is clearly vital the evidence on how best to achieve this is limited. While the National Health Service (NHS) is currently undergoing major reform, attention needs to be paid to designing better ways to improve the current disconnect between primary and secondary care. This should then help to improve physical, psychological and social outcomes for individuals with MMI.

The Role of Cannabinoids in the Neurobiology of Sensory Gating: A firing rate model study

Gating of sensory (e.g. auditory) information has been demonstrated as a reduction in the auditory-evoked potential responses recorded in the brain of both normal animals and human subjects. Auditory gating is perturbed in schizophrenic patients and pharmacologically by drugs such as amphetamine, phencyclidine or ketamine, which precipitate schizophrenic-like symptoms in normal subjects. The neurobiological basis underlying this sensory gating can be investigated using local field potential recordings from single electrodes. In this paper we use such technology to investigate the role of cannabinoids in sensory gating. Cannabinoids represent a fundamentally new class of retrograde messengers which are released postsynaptically and bind to presynaptic receptors. In this way they allow fine-tuning of neuronal response, and in particular can lead to so-called depolarization-induced suppression of inhibition (DSI). Our experimental results show that application of the exogenous cannabinoid WIN55, 212-2 can abolish sensory gating as measured by the amplitude of local field responses in rat hippocampal region CA3. Importantly we develop a simple firing rate population model of CA3 and show that gating is heavily dependent upon the presence of a slow inhibitory (GABAB) pathway. Moreover, a simple phenomenological model of cannabinoid dynamics underlying DSI is shown to abolish gating in a manner consistent with our experimental findings.

In vitro studies of drug transformations: application to forensic toxicology

The forensic toxicologist faces challenges in the detection of drugs and poisons in biological samples due to transformations which occur both during life and after death. For example, changes can result from drug metabolism during life or from the use of formalin solution for post mortem embalming purposes. The former requires the identification of drug metabolites and the latter the identification of chemical reaction products in order to know which substances had been administered. The work described in this thesis was aimed at providing ways of tackling these challenges and was divided into two parts. Part 1 investigated the use of in vitro drug metabolism by human liver microsomes (HLM) to obtain information on drug metabolites and Part 2 investigated the chemical reactions of drugs and a carbamate pesticide with formalin solution and formalin-blood. The initial aim of part I was to develop an in vitro metabolism method using HLM, based on a literature review of previous studies of this type. MDMA was chosen as a model compound to develop the HLM method because its metabolism was known and standards of its metabolites were commercially available. In addition, a sensitive and selective method was developed for the identification and quantitation of hydrophilic phase I drug metabolites using LC/MS/MS with a conventional reverse-phase (C18) column. In order to obtain suitable retention factors for polar drug metabolites on this column, acetyl derivatives were evaluated for converting the metabolites to more lipophilic compounds and an optimal separation system was developed. Acetate derivatives were found to be stable in the HPLC mobile phase and to provide good chromatographic separation of the target analytes. In vitro metabolism of MDMA and, subsequently, of other drugs involved incubation of 4 µg drug substance in pH 7.4 buffer with an NADPH generating system (NGS) at 37oC for 90 min with addition of more NGS after 30 min. The reaction was stopped at 90 min by the addition of acetonitrile before extraction of the metabolites. Acetate derivatives of MDMA metabolites were identified by LC/MS/MS using multiple reaction monitoring (MRM). Three phase I metabolites (both major and minor metabolites) of MDMA were detected in HLM samples. 3,4-dihydroxy-methamphetamine and 4-hydroxy-3-methoxymethamphetamine were found to be major metabolites of MDMA whereas 3,4-methylenedioxyamphetamine was found to be a minor metabolite. Subsequently, ten MDMA positive urines were analysed to compare the metabolite patterns with those produced by HLM. An LC/MS method for MDMA and its metabolites in urine samples was developed and validated. The method demonstrated good linearity, accuracy and precision and insignificant matrix effects, with limits of quantitation of 0.025 µg/ml. Moreover, derivatives of MDMA and its metabolites were quantified in all 10 positive human urine samples. The urine metabolite pattern was found to be similar to that from HLM. The second aim of Part 1 was to use the HLM system to study the metabolism of some new psychoactive substances, whose misuse worldwide has necessitated the development of analytical methods for these drugs in biological specimens. Methylone and butylone were selected as representative cathinones and para-methoxyamphetamine (PMA) was chosen as a representative ring-substituted amphetamine, because of the involvement of these drugs in recent drug-related deaths, because of a relative lack of information on their metabolism, and because reference standards of their metabolites were not commercially available. An LC/MS/MS method for the analysis of methylone, butylone, PMA and their metabolites was developed. Three phase I metabolites of methylone and butylone were detected in HLM samples. Ketone reduction to β-OH metabolites and demethylenation to dihydroxy-metabolites were found to be major phase I metabolic pathways of butylone and methylone whereas N-demethylation to nor-methylone and nor-butylone were found to be minor pathways. Also, demethylation to para-hydroxyamphetamine was found to be a major phase I metabolic pathway of PMA whereas β-hydroxylation to β-OH-PMA was found to be a minor pathway. Formaldehyde is used for embalming, to reduce decomposition and preserve cadavers, especially in tropical countries such as Thailand. Drugs present in the body can be exposed to formaldehyde resulting in decreasing concentrations of the original compounds and production of new substances. The aim of part II of the study was to evaluate the in vitro reactions of formaldehyde with selected drug groups including amphetamines (amphetamine, methamphetamine and MDMA), benzodiazepines (alprazolam and diazepam), opiates (morphine, hydromorphone, codeine and hydrocodone) and with a carbamate insecticide (carbosulfan). The study would identify degradation products to serve as markers for the parent compounds when these were no longer detectable. Drugs standards were spiked in 10% formalin solution and 10% formalin blood. Water and whole blood without formalin were used for controls. Samples were analysed by LC/MS/MS at different times from the start, over periods of up to 30 days. Amphetamine, methamphetamine and MDMA were found to rapidly convert to methamphetamine, DMA and MDDMA respectively, in both formalin solution and formalin blood, confirming the Eschweiler-Clarke reaction between amine-containing compounds and formaldehyde. Alprazolam was found to be unstable whereas diazepam was found to be stable in both formalin solution and water. Both were found to hydrolyse in formalin solution and to give open-ring alprazolam and open-ring diazepam. Other alprazolam conversion products attached to paraformaldehyde were detected in both formalin solution and formalin blood. Morphine and codeine were found to be more stable than hydromorphone and hydrocodone in formalin solution. Conversion products of hydromorphone and hydrocodone attached to paraformaldehyde were tentatively identified in formalin solution. Moreover, hydrocodone and hydromorphone rapidly decreased within 24 h in formalin blood and could not be detected after 7 days. Carbosulfan was found to be unstable in formalin solution and was rapidly hydrolysed within 24 h, whereas in water it was stable up to 48 h. Carbofuran was the major degradation product, plus smaller amounts of other products, 3-ketocarbofuran and 3-hydrocarbofuran. By contrast, carbosulfan slowly hydrolysed in formalin-blood and was still detected after 15 days. It was concluded that HLM provide a useful tool for human drug metabolism studies when ethical considerations preclude their controlled administration to humans. The use of chemical derivatisation for hydrophilic compounds such as polar drug metabolites for analysis by LC/MS/MS with a conventional C18 column is effective and inexpensive, and suitable for routine use in the identification and quantitation of drugs and their metabolites. The detection of parent drugs and their metabolites or conversion and decomposition products is potentially very useful for the interpretation of cases in forensic toxicology, especially when the original compounds cannot be observed.

Neurobiology and clinical implications of lucid dreaming

Several lines of evidence converge to the idea that rapid eye movement sleep (REMS) is a good model to foster our understanding of psychosis. Both REMS and psychosis course with internally generated perceptions and lack of rational judgment, which is attributed to a hyperlimbic activity along with hypofrontality. Interestingly, some individuals can become aware of dreaming during REMS, a particular experience known as lucid dreaming (LD), whose neurobiological basis is still controversial. Since the frontal lobe plays a role in self-consciousness, working memory and attention, here we hypothesize that LD is associated with increased frontal activity during REMS. A possible way to test this hypothesis is to check whether transcranial magnetic or electric stimulation of the frontal region during REMS triggers LD. We further suggest that psychosis and LD are opposite phenomena: LD as a physiological awakening while dreaming due to frontal activity, and psychosis as a pathological intrusion of dream features during wake state due to hypofrontality. We further suggest that LD research may have three main clinical implications. First, LD could be important to the study of consciousness, including its pathologies and other altered states. Second, LD could be used as a therapy for recurrent nightmares, a common symptom of depression and post-traumatic stress disorder. Finally, LD may allow for motor imagery during dreaming with possible improvement of physical rehabilitation. In all, we believe that LD research may clarify multiple aspects of brain functioning in its physiological, altered and pathological states.

El dolor en la enfermedad de Parkinson. Implicaciones autonómicas y afectivas

Introducción y objetivo: La enfermedad de Parkinson (EP) es una enfermedad neurodegenerativa, la segunda con mayor prevalencia, después de la enfermedad de Alzheimer (EA). La enfermedad presenta tanto síntomas motores como “no motores”, entre los que se encuentra disfunción autonómica, dolor, deterioro cognitivo, ansiedad, depresión, entre otros. El dolor en la EP, a pesar de su frecuencia, sigue siendo un síntoma infravalorado, infradiagnosticado e infratratado. Nuestro objetivo principal es evaluar la frecuencia y configuración del dolor en la EP y sus implicaciones afectivas y autonómicas. Pacientes, material y métodos: Estudio multicéntrico, transversal, de carácter retrospectivo y prospectivo. Se incluyeron 407 pacientes con enfermedad de Parkinson (EP) de los que un 70% estaban en una situación leve-moderada (estadios 2 o 3 de Hoehn y Yahr), con edad media de 65,01 años y 7,07 años de duración de la EP. Se administraron las escalas SCOPA-Motor, SCOPA-Autonómica, SCOPA-Cog, Parkinson’s Psychosis Rating Scale modificada, Hoehn & Yarh, las Escala Hospitalaria de Ansiedad y Depresión, Dolor (EVA frecuencia), EQ-5D y estudios neurofisiológicos específicos de Sistema Nervioso Autónomo (SNA). El análisis estadístico se ha realizado con el programa de cálculo estadístico SPSS versión 22. Resultados: En nuestro estudio encontramos una prevalencia del dolor elevada (72%) y los pacientes afirman mayoritariamente (79,2%) que su dolor tiene relación con la EP. La duración de la enfermedad se correlaciona con la intensidad y frecuencia del dolor (dolor intensidad: r: 0,138; p< 0,01; dolor frecuencia: r: 0,168; p< 0,01 ). A mayor evolución de la EP mayor es la percepción del dolor. El 60% de los pacientes de EP manifiestan sentir dolor cuando aparecen episodios de rigidez y tirantez en alguno de los miembros superiores o inferiores frente a un 40% que no. Curiosamente un número mayor (el 76% de los pacientes) siente dolor durante los episodios de discinesias frente a un 24% que no lo percibe. Sin embargo, en la EP el dolor se relaciona más con la situación afectiva que con la motora, como hemos podido demostrar la relación entre el Dolor Total y la HADS (Depresión) Total y la Escala Hoehn & Yahr. El coeficiente de contingencia es mayor en la depresión (C: 0,894; N=403) que en la situación motora (C: 0,637; N=401). El dolor evoluciona y se percibe de forma paralela a otros síntomas no motores (ánimo, nicturia, alteración del control vesical, estreñimiento, etc.) pero con lo que se relaciona más es con la situación afectiva del paciente parkinsoniano (ansiedad (r: 0,40; p < 0,01), depresión (r: 0.28; p < 0,01). La mayor asociación se encuentra entre la ansiedad y el dolor, seguida de la depresión y en menor grado nicturia y sialorrea. Existe una correlación positiva entre las dos subescalas de la HADS (depresión y ansiedad). Existe una alta prevalencia de alteración de la memoria inmediata como síntoma “no motor” (SNM) en nuestra serie (96,5%). En base a nuestros resultados el sexo femenino se asocia al dolor en la EP. Con respecto a la fenomenología el dolor en la EP es muy variable. Se percibe con mayor frecuencia como una corriente eléctrica (64%), calor (60%), frialdad (60%), punzante (52%), difuso (52%), interno (40%), acorchamiento u hormigueo (40%), La frecuencia de la cantidad de tipos de dolor es la siguiente: un tipo de dolor (12%), dos tipos de dolores (16%) y tres tipos de dolores (72%). La media de tipos de dolor en nuestro estudio es superior a 2 tipos (x ̅: 2,60 ± 0,63; rango: 1-3). En los casos que toman levodopa les sigue unas tres cuartas partes que lo perciben como palpitante, tirante, punzante. En los casos que toman agonista dopaminérgico lo perciben en un 75% como adormecimiento, interno, descarga eléctrica, frialdad y calor. El dolor en la EP respecto a su configuración es multimodal. Los parámetros neurofisiológicos están relacionados con los umbrales de dolor. La actividad simpática y la sensibilidad nociceptiva están disminuidas en la EP. Los enfermos con EP tienen un umbral menor para el frío según los datos del estudio del Cold-Ice. En lo referente a la terapéutica el tratamiento dopaminérgico es eficaz para el control del dolor en el 48% de los pacientes mientras que el tratamiento analgésico estándar prescrito mejora el dolor en un 78,8%. Por último, casi la mitad de la población de nuestro estudio (47,52%) evaluada con la EQ-5D tiene problemas en alguna de las dimensiones de la calidad de vida. Hay una relación positiva entre la escala analógica visual del dolor (EVA) y la EQ-5D que evalúa la CVRS y entre la intensidad de dolor y la CVRS (r:-0,298; p < 0,01). Es decir, una mayor vivencia de dolor empeora la CVRS del paciente con EP. Conclusiones: En la enfermedad de Parkinson el dolor es un síntoma no motor de elevada prevalencia, íntimamente relacionado con la afectación de los sistemas afectivos y autonómicos medido con test neuro-vegetativos específicos. El presente estudio confirma su relación con el lado más afecto de la enfermedad, las fluctuaciones motoras, el tiempo de evolución, con la situación anímica (depresión y ansiedad) y con el sexo femenino, así como su carácter multimodal y gran variedad de expresión sintomática. Es muy llamativa su asociación con el déficit mnésico. Por último esta vivencia repercute en forma llamativa en la calidad de vida relacionada con la salud por lo que sería importante conocer y manejar mejor estos aspectos de la enfermedad de Parkinson.

Perspectiva dinâmica da melancolia: O vazio branco e frio que congela na ausência da presença do objecto

Dissertação de Mestrado apresentada no Instituto Superior de Psicologia Aplicada para obtenção do grau de Mestre na especialidade de Psicologia Clínica

The Hitchcok boy: treating aggressive acting out in child therapy

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Retour post-isolement en milieu psychiatrique : développement, implantation et évaluation d’une intervention en soins aigus

L’isolement avec ou sans contention (IC) en milieu psychiatrique touche près d’un patient sur quatre au Québec (Dumais, Larue, Drapeau, Ménard, & Giguère-Allard, 2011). Il est pourtant largement documenté que cette pratique porte préjudice aux patients, aux infirmières et à l’organisation (Stewart, Van der Merwe, Bowers, Simpson, & Jones, 2010). Cette mesure posant un problème éthique fait l’objet de politiques visant à la restreindre, voire à l’éliminer. Les études sur l’expérience de l’isolement du patient de même que sur la perception des infirmières identifient le besoin d'un retour sur cet évènement. Plusieurs équipes de chercheurs proposent un retour post-isolement (REPI) intégrant à la fois l’équipe traitante, plus particulièrement les infirmières, et le patient comme intervention afin de diminuer l’incidence de l’IC. Le REPI vise l’échange émotionnel, l’analyse des étapes ayant mené à la prise de décision d’IC et la projection des interventions futures. Le but de cette étude était de développer, implanter et évaluer le REPI auprès des intervenants et des patients d’une unité de soins psychiatriques aigus afin d’améliorer leur expérience de soins. Les questions de recherche étaient : 1) Quel est le contexte d’implantation du REPI? 2) Quels sont les éléments facilitants et les obstacles à l’implantation du REPI selon les patients et les intervenants? 3) Quelle est la perception des patients et des intervenants des modalités et retombées du REPI?; et 4) L’implantation du REPI est-elle associée à une diminution de la prévalence et de la durée des épisodes d’IC? Cette étude de cas instrumentale (Stake, 1995, 2008) était ancrée dans une approche participative. Le cas était celui de l’unité de soins psychiatriques aigus pour premier épisode psychotique où a été implanté le REPI. En premier lieu, le développement du REPI a d’abord fait l’objet d’une documentation du contexte par une immersion dans le milieu (n=56 heures) et des entretiens individuels avec un échantillonnage de convenance (n=3 patients, n=14 intervenants). Un comité d’experts (l’étudiante-chercheuse, six infirmières du milieu et un patient partenaire) a par la suite développé le REPI qui comporte deux volets : avec le patient et en équipe. L’évaluation des retombées a été effectuée par des entretiens individuels (n= 3 patients, n= 12 intervenants) et l’examen de la prévalence et de la durée des IC six mois avant et après l’implantation du REPI. Les données qualitatives ont été examinées selon une analyse thématique (Miles, Huberman, & Saldana, 2014), tandis que les données quantitatives ont fait l’objet de tests descriptifs et non-paramétriques. Les résultats proposent que le contexte d’implantation est défini par des normes implicites et explicites où l’utilisation de l’IC peut générer un cercle vicieux de comportements agressifs nourris par un profond sentiment d’injustice de la part des patients. Ceux-ci ont l’impression qu’ils doivent se conformer aux attentes du personnel et aux règles de l’unité. Les participants ont exprimé le besoin de créer des opportunités pour une communication authentique qui pourrait avoir lieu lors du REPI, bien que sa pratique soit variable d’un intervenant à un autre. Les résultats suggèrent que le principal élément ayant facilité l’implantation du REPI est l’approche participative de l’étude, alors que les obstacles rencontrés relèvent surtout de la complexité de la mise en œuvre du REPI en équipe. Lors du REPI avec le patient, les infirmières ont pu explorer ses sentiments et son point de vue, ce qui a favorisé la reconstruction de la relation thérapeutique. Quant au REPI avec l’équipe de soins, il a été perçu comme une opportunité d’apprentissage, ce qui a permis d’ajuster le plan d’intervention des patients. Suite à l’implantation du REPI, les résultats ont d’ailleurs montré une réduction significative de l’utilisation de l’isolement et du temps passé en isolement. Les résultats de cette thèse soulignent la possibilité d’outrepasser le malaise initial perçu tant par le patient que par l’infirmière en systématisant le REPI. De plus, cette étude met l’accent sur le besoin d’une présence authentique pour atteindre un partage significatif dans la relation thérapeutique, ce qui est la pierre d’assise de la pratique infirmière en santé mentale. Cette étude contribue aux connaissances sur la prévention des comportements agressifs en milieu psychiatrique en documentant le contexte dans lequel se situe l’IC, en proposant un REPI comportant deux volets de REPI et en explorant ses retombées. Nos résultats soutiennent le potentiel du développement d’une prévention tertiaire qui intègre à la fois la perspective des patients et des intervenants.

Perfil conductual de las drogas de diseño MBDB, MDEA y PMA en modelos animales de agresión y ansiedad

MBDB, MDEA y PMA son tres drogas de diseño, estructuralmente similares al MDMA (“éxtasis”), que se han identificado en la composición de pastillas distribuidas como “éxtasis” en entornos recreativos durante los últimos treinta años. Estas feniletilaminas sintéticas presentan un perfil psicotrópico de tipo entactógeno (con capacidad para facilitar la proximidad, el contacto y la comunicación empática), similar al del MDMA en el modelo de discriminación de drogas. El MDMA ha sido objeto de un creciente interés científico y es, hasta la fecha, la única sustancia con un perfil entactógeno de la que se han investigado sus efectos conductuales en modelos animales de agresión y ansiedad, si bien sus resultados no siempre coinciden. Aunque existen algunas evidencias de que el MDMA puede tener efectos ansiolíticos en animales de laboratorio (Lin, Burden, Christie, & Johnston, 1999; Morley & McGregor, 2000; Ho, Pawlak, Guo, & Schwarting, 2004), en otros estudios se han observado alteraciones conductuales y correlatos neuroquímicos que sugieren un efecto ansiogénico (Bhattacharya, Bhattacharya & Ghosal, 1998; Gurtman, Morley, Li, Hunt, & McGregor, 2002; Maldonado & Navarro, 2000;; Navarro & Maldonado, 2002). Asimismo, en otros trabajos se ha señalado que el MDMA induce efectos antiagresivos (reducción de las conductas de amenaza y ataque), que se acompañan de un marcado aumento de las conductas de evitación/huida y defensa/sumisión, así como de una reducción de las conductas de investigación social, sugiriendo también la existencia de un perfil ansiogénico en los encuentros agonísticos entre ratones machos (Maldonado & Navarro, 2001; Navarro & Maldonado, 1999). En contraste, hasta la fecha la información experimental de las drogas MBDB, MDEA y PMA se limita a la evaluación de sus efectos conductuales sobre la conducta motora, así como algunos estudios sobre su metabolismo y posible mecanismo de acción. El objetivo general de este trabajo de investigación ha sido estudiar el perfil conductual de MBDB, MDEA y PMA en modelos animales de agresión y ansiedad. Para ello, se han examinado los efectos del MBDB (2, 4 y 8 mg/kg), MDEA (5, 10 y 20 mg/kg) y PMA (2, 4, 8 y 12 mg/kg) utilizando el modelo de agresión inducida por aislamiento y el modelo de ansiedad del laberinto elevado en cruz en ratones machos. Los resultados indican que estas sustancias en general comparten un perfil antiagresivo inespecífico. Esta falta de especificidad se debe en unos casos al aumento de las conductas de inmovilidad (4-12 mg/kg PMA), pero también a la presencia de propiedades ansiogénicas durante la interacción social, en especial con dosis elevadas, mientras que solo las dosis más bajas parecen aumentar la proximidad social, en especial la dosis menor de MBDB. Además, estas drogas parecen alterar el patrón conductual agonístico ofensivo (MBDB y MDEA) y defensivo (MBDB, MDEA y PMA), produciendo cambios diádicos que resultan coherentes con un aumento del nivel de conflicto y de ansiedad. En consonancia, los resultados del modelo del laberinto elevado en cruz indican que el MBDB produce un aumento de la ansiedad de menor intensidad que el producido por el MDMA. Sin embargo, MDEA y PMA parecen generar un estado de hipoexploración, y solo en dosis determinadas (20 mg/kg de MDEA y 4 mg/kg de PMA) muestran alteraciones discretas que sugieren un efecto ansiogénico débil, un perfil que en conjunto podría sugerir cierta similitud con alteraciones conductuales propias de los compuestos alucinógenos. Debido a la diferencia del perfil conductual del MDEA y PMA hallados en ambos modelos, sería necesario evaluar la ansiedad y su posible relación con la dosis y/o con la presencia de un oponente en la prueba en otros modelos experimentales. Lin, H. Q., Burden, P. M., Christie, M. J., & Johnston, G. A. R. (1999). The anxiogenic-like and anxiolytic-like effects of MDMA on mice in the elevated plus-maze: A comparison with amphetamine. Pharmacology, Biochemistry and Behavior, 62(3), 403-408. Morley, K. C., & McGregor, I. S. (2000). (±)-3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') increases social interaction in rats. European Journal of Pharmacology, 408(1), 41-49. Bhattacharya, S. K., Bhattacharya, A., & Ghosal, S. (1998). Anxiogenic activity of methylenedioxymethamphetamine (Ecstasy): An experimental study. Biogenic Amines, 14(3), 217-237. Gurtman, C. G., Morley, K. C., Li, K. M., Hunt, G. E., & McGregor, I. S. (2002). Increased anxiety in rats after 3,4-methylenedioxymethamphetamine: Association with serotonin depletion. European Journal of Pharmacology, 446(1-3), 89-96. Ho, Y., Pawlak, C. R., Guo, L., & Schwarting, R. K. W. (2004). Acute and long-term consequences of single MDMA administration in relation to individual anxiety levels in the rat. Behavioural Brain Research, 149(2), 135-144. Maldonado, E., & Navarro, J. F. (2000). Effects of 3,4-methylenedioxy-methamphetamine (MDMA) on anxiety in mice tested in the light/dark box. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 24(3), 463-472. Maldonado, E., & Navarro, J. F. (2001b). MDMA ('ecstasy') exhibits an anxiogenic-like activity in social encounters between male mice. Pharmacological Research, 44(1), 27-31. Navarro, J. F., & Maldonado, E. (1999). Behavioral profile of 3,4-methylenedioxy-methamphetamine (MDMA) in agonistic encounters between male mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 23(2), 327-334. Navarro, J. F., & Maldonado, E. (2002). Acute and subchronic effects of MDMA ("ecstasy") on anxiety in male mice tested in the elevated plus-maze. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 26(6), 1151-1154.

Estudo de um caso de psicose branca

Dissertação de Mestrado apresentada no Instituto Superior de Psicologia Aplicada para obtenção de grau de Mestre na especialidade de Psicologia Clínica

An investigation into the suitability of time-of-flight mass spectrometry in forensic toxicology

Liquid chromatography coupled with mass spectrometry is one of the most powerful tools in the toxicologist’s arsenal to detect a wide variety of compounds from many different matrices. However, the huge number of potentially abused substances and new substances especially designed as intoxicants poses a problem in a forensic toxicology setting. Most methods are targeted and designed to cover a very specific drug or group of drugs while many other substances remain undetected. High resolution mass spectrometry, more specifically time-of-flight mass spectrometry, represents an extremely powerful tool in analysing a multitude of compounds not only simultaneously but also retroactively. The data obtained through the time-of-flight instrument contains all compounds made available from sample extraction and chromatography, which can be processed at a later time with an improved library to detect previously unrecognised compounds without having to analyse the respective sample again. The aim of this project was to determine the utility and limitations of time-of-flight mass spectrometry as a general and easily expandable screening method. The resolution of time-of-flight mass spectrometry allows for the separation of compounds with the same nominal mass but distinct exact masses without the need to separate them chromatographically. To simulate the wide variety of potentially encountered drugs in such a general screening method, seven drugs (morphine, cocaine, zolpidem, diazepam, amphetamine, MDEA and THC) were chosen to represent this variety in terms of mass, properties and functional groups. Consequently, several liquid-liquid and solid phase extractions were applied to urine samples to determine the most general suitable and unspecific extraction. Chromatography was optimised by investigating the parameters pH, concentration, organic solvent and gradient of the mobile phase to improve data obtained by the time-of-flight instrument. The resulting method was validated as a qualitative confirmation/identification method. Data processing was automated using the software TargetAnalysis, which provides excellent analyte recognition according to retention time, exact mass and isotope pattern. The recognition of isotope patterns allows excellent recognition of analytes even in interference rich mass spectra and proved to be a good positive indicator. Finally, the validated method was applied to samples received from the A& E Department of Glasgow Royal Infirmary in suspected drug abuse cases and samples received from the Scottish Prison Service, which we received from their own prevalence study targeting drugs of abuse in the prison population. The obtained data was processed with a library established in the course of this work.

Aportes a la revisión de literatura sobre la relación entre el arte y la psicosis desde una perspectiva psicoanalítica.

El presente trabajo tiene como propósito hacer una revisión crítica de dos de los trabajos más relevantes que abordan la relación entre salud mental y arte, a saber: Artistry of the Mentally Ill, de Hans Prinzhorn (1922/1972) y Madness and Art, de Walter Morgenthaler (1921/1992). Para ello, se presenta primero un recuento de estos textos, y en un segundo momento, su respectivo análisis. De esta manera, llevo a cabo una revisión crítica de los ya mencionados libros a la luz de diferentes teorías psicoanalíticas que abordan algunos temas cruciales dentro de esta relación, como lo son la psicosis, y desde otras perspectivas, el arte marginal y la creatividad, aportando así a la investigación teórica de este tema particular.

Accompanied selfrehabilitation

"Every once in a great while, there arises a young psychiatrist with entirely new rehabilitation ideas for helping patients retrieve their lives from psychosiso Usually such ideas initially cause significant negative reactions from peers but a handful of sturdy physicians continued on to show the world that something different is possible such as George Brooks of Vermont in the U.S., E.E. Antinnen of Finland, and Franco Basaglia of Italy. Now we have to add to this illustrious list, the name of Alberto Fergusson of Colombia, South America". (Extrae of the "Forward") Prof Courtenay M. Harding

Cartas imaginarias a Freud y otros ensayos

"Las cinco cartas imaginarias a Freud recogidas en este libro son su columna vertebral y los efectos que producirán en la comunidad psicoanalítica están aún por verse. Pero las cartas no agotan los aportes de esta obra. Alberto Fergusson, médico, psiquiatra y psicoanalista, tiene toda una historia vital dedicada al estudio y el tratamiento de pacientes psicóticos. En los años ochenta creó el Instituto de Autorrehabilitación Acompañada, inspirado en las premisas del freudomarxismo de la Escuela de Frankfurt y en el mal llamado "movimiento antipsiquiátrico" (mal llamado en la medida en que no se opone a la psiquiatría, sino más bien a una mala práctica psiquiátrica) y en los trabajos y experiencias de Laing, Cooper, Basaglia y Szasz. La materialización de los conceptos del Instituto se produjo en una singular experiencia denominada Fungrata, pero conocida en el mundo académico y profesional como "La granja". Esa institución, pionera en nuestro país, sigue produciendo asombro en varias partes del mundo por haber llegado, desde ya hace décadas, adonde muchos otros dispositivos dedicados a la intervención psicosocial con pacientes psicóticos hoy aspiran llegar". (Extracto del "prólogo") Miguel Gutiérrez-Peláez