The utilization of chiral ion mobility spectrometry for the detection of enantiomeric mixtures and thermally labile compounds

This dissertation utilized electrospray ion mobility mass spectrometry (ESI-IMS-MS) to develop methods necessary for the separation of chiral compounds of forensic interest. The compounds separated included ephedrines and pseudoephedrines, that occur as impurities in confiscated amphetamine type substances (ATS) in an effort to determine the origin of these substances. The ESI-IMS-MS technique proved to be faster and more cost effective than traditional chromatographic methods currently used to conduct chiral separations such as gas and liquid chromatography. Both mass spectrometric and computational analysis revealed the separation mechanism of these chiral interactions allowing for further development to separate other chiral compounds by IMS. Successful separation of chiral compounds was achieved utilizing a variety of modifiers injected into the IMS drift tube. It was found that the modifiers themselves did not need to be chiral in nature and that achiral modifiers were sufficient in performing the required separations. The ESI-IMS-MS technique was also used to detect thermally labile compounds which are commonly found in explosive substances. The methods developed provided mass spectrometric identification of the type of ionic species being detected from explosive analytes as well as the appropriate solvent that enhances detection of these analytes in either the negative or positive ion mode. An application of the developed technique was applied to the analysis of a variety of low explosive smokeless powder samples. It was found that the developed ESI-IMS-MS technique not only detected the components of the smokeless powders, but also provided data that allowed the classification of the analyzed smokeless powders by manufacturer or make. ^

Design and protocol for the Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial : a randomised controlled trial

Acknowledgements Thank you to all the participants who agreed to take part in the trial. This study was supported NHS Research Scotland (NRS), through Chief Scientist Office (CSO) and the Scottish Mental Health Research Network, and the Clinical Research Network-Mental Health. We are grateful to the Psychosis Research Unit (PRU) Service User Reference Group (SURG) for their consultation regarding the design of the study and contribution to the developments of study related materials. We are grateful to our Independent Trial Steering Committee and Independent Data Monitoring Committee for provided oversight of the trial. Funding This project was funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) programme (project number10/101/02) and will be published in full in Health Technology Assessment. Visit the HTA programme website for further project information. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health.

Investigating the developmental and behavioral consequences of maternal immune activation on affected offspring

Maternal infection during pregnancy increases the risk of several neuropsychiatric disorders later in life, many of which have a component of dopaminergic (DA) dysfunction, including schizophrenia, autism spectrum disorders (ASD), and attention deficit hyperactivity disorder (ADHD). The majority of DA neurons are found in the adult midbrain; as such the midbrain is a key region of interest regarding these disorders. The literature is conflicting regarding the behavioral alterations following maternal immune activation (MIA) exposure, and the cellular and molecular consequences of MIA on the developing midbrain remain to be fully elucidated. Thus, this thesis aimed to establish the consequences of acute and mild MIA on offspring dopamine-related behaviors, as well as the associated cellular and molecular disturbances of MIA on offspring midbrains. We utilized a rat model of MIA using low dose (50μg/kg, I.P.) of LPS administered at different gestational ages. Our first study indicated that MIA at later gestational ages significantly increased pro-inflammatory IL-1β expression, and reduced HSD11B2 expression in the placenta, which is an important regulator of fetal development. In utero LPS exposure at later gestational ages also impaired the growth of neurons from affected offspring. This study identified key gestational stages during which MIA resulted in differential effects. We utilized these time points in subsequent studies, the next of which investigated neurobehavioral outcomes following MIA. Our results from that study showed that motor differences occurred in juvenile offspring following MIA at E16 only, and these differences were compensated for in adolescence. Then, there was a decline in motor behavior capabilities in adulthood, again only for animals exposed to MIA on E16 (and not E12). Furthermore, our results also demonstrated adolescent and adult offspring that were exposed to MIA at E12 had diminished responses to amphetamine in reward seeking behaviors. In our final study, we aimed to investigate the molecular and cellular changes following MIA which might explain these behavioral alterations. This final study showed a differential inflammatory response in fetal midbrains depending on gestational age of exposure as well as differential developmental alterations. For example, LPS exposure at E16 resulted in decreased VM neurosphere size after 7DIV and this was associated with an increased susceptibility to neurotoxic effects of pro-inflammatory cytokines for VM neurospheres and VM DA neurons treated in culture. In utero LPS exposure at E16 also reduced DA neuron count of fetal VM, measured by TH staining. However, there were no differences in DA neuron number in juvenile, adolescent, or adult offspring. Similarly, LPS exposure did not alter cell number or morphology of glial cells in the midbrains of affected offspring. In conclusion, this thesis indicated later rat pregnancy (E16) as vulnerable time for MIA to affect the development of the nigrostriatal pathway and subsequent behavioral outcomes, possibly implicating a role for MIA in increased risk for disorders associated with motor behavior, like PD. These effects may be mediated through alterations in the placenta and altered inflammatory mediators in the offspring brain. This thesis has also shown that MIA in earlier rat pregnancy (E12) results in altered mesocorticolimbic function, and in particular MIA on E12 resulted in a differential response to amphetamine in affected offspring, which may implicate a role for MIA in increasing the risk for disorders associated with this pathway, including drug tolerance and addiction.

The Relationship Between Self-Awareness and Psychotic-Like Experiences

The psychosis phenotype is thought to exist on a continuum, such that the same symptoms experienced by individuals diagnosed with psychotic disorders can also manifest in the general population to a less severe degree. The subclinical psychotic-like experiences reported by healthy individuals share a number of risk factors with psychotic disorders and confer greater risk of developing a psychotic disorder. Thus, healthy individuals with psychotic-like experiences comprise a valid population in which to study the underlying mechanisms of clinically significant psychotic symptoms. In this thesis, we aimed to further our understanding of psychotic-like experiences and the individuals who report them. We explored the relationships between tasks measuring different aspects of self-awareness and self-reported psychotic-like experiences using data obtained from 30 university students. We found that greater sensitivity to the difference between one’s own voice and another person’s voice predicted fewer symptoms of persecutory ideation. Additionally, we found that greater tendency to misattribute one’s own voice to an external source predicted greater symptoms of persecutory ideation.

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.

Núcleo Psicótico numa Psicose em Potencial Complexo de Mãe Morta e Psicose Branca: um estudo de caso

Este estudo teve como objetivo principal explorar dois conceitos importantes na teoria do psicanalista francês André Green: complexo de mãe morta e psicose branca. A decatexia provocada pelo afastamento emocional materno (complexo de mãe morta), induz um vazio interior (angústia branca). Esta sensação de vazio, de paragem, uma depressão sem afetos e a alucinação negativa, são manifestações da psicose branca (estrutura matriz onde se observa o núcleo da psicose sem que esta necessariamente se manifeste). O método utilizado foi o estudo de caso, de um sujeito do sexo masculino em regime de internamento. Os instrumentos de avaliação incluem a técnica projetiva de Rorschach (aplicada no início e no final do internamento) e o Thematic Apperception Test (aplicado no início do internamento). Através do material colhido em contexto de acompanhamento individual e das técnicas projetivas observaram-se pontos de contacto entre o conceito de psicose branca de Green, falso self de Winnicott e as personalidades “as if” de Helene Deutsch. A morte metafórica da mãe, o seu afastamento emocional, poderá estar na origem destas perturbações, onde se observa o núcleo da psicose. Nestas situações clínicas, em que o vazio interno predomina, a prática psicoterapêutica requer um posicionamento particular do clínico, que não deve estar nem muito próximo (sentido como intrusivo) nem muito distante (sentido como abandónico) do seu paciente. / This work had the purpose of exploring two important concepts in the theory of the French psychoanalyst André Green: the dead mother complex and the blank psychosis. The decathexis caused by a maternal emotional withdrawal (dead mother complex) induces an internal void (blank anguish). This feeling of emptiness, stoppage, a depression without affects and the negative hallucination are manifestations of blank psychosis (a matrix structure where one can observe the psychotic kernel, even though without having a manifest psychosis). The applied method was the case study, with a young male institutionalized subject, and to support it we used the Thematic Apperception Test (applied in the early phases of treatment) and the Rorschach projective technique (applied at the beginning and ending of the treatment). Through the data collected in the therapeutic sessions and the projective techniques applied, we observed points of contact between blank psychosis, Winnicott`s False Self and Helene Deutsch “as if” personalities. The mother’s metaphorical death, her emotional withdrawal, could be in the genesis of these disturbances, where we can observe the psychotic kernel. When we are dealing with this kind of patient, where the internal void prevails, the psychotherapeutic technique requires a special positioning from the therapist in relation to the patient, that shouldn’t be too close (experienced as intrusive), nor too distant (experienced with feelings of abandonment).

Mémoire de source, propension à halluciner et psychose : identification de marqueurs cognitifs et cliniques chez une population à haut risque génétique

Les déficits cognitifs sont centraux à la psychose et sont observables plusieurs années avant le premier épisode psychotique. L’atteinte de la mémoire épisodique est fréquemment identifiée comme une des plus sévères, tant chez les patients qu’avant l’apparition de la pathologie chez des populations à risque. Chez les patients psychotiques, l’étude neuropsychologique des processus mnésiques a permis de mieux comprendre l’origine de cette atteinte. Une altération des processus de mémoire de source qui permettent d’associer un souvenir à son origine a ainsi été identifiée et a été associée aux symptômes positifs de psychose, principalement aux hallucinations. La mémoire de source de même que la présence de symptômes sous-cliniques n’ont pourtant jamais été investiguées avant l’apparition de la maladie chez une population à haut risque génétique de psychose (HRG). Or, leur étude permettrait de voir si les déficits en mémoire de source de même que le vécu d’expériences hallucinatoires sont associés à l’apparition de la psychose ou s’ils en précèdent l’émergence, constituant alors des indicateurs précoces de pathologie. Afin d’étudier cette question, trois principaux objectifs ont été poursuivis par la présente thèse : 1) caractériser le fonctionnement de la mémoire de source chez une population HRG afin d’observer si une atteinte de ce processus précède l’apparition de la maladie, 2) évaluer si des manifestations sous-cliniques de symptômes psychotiques, soit les expériences hallucinatoires, sont identifiables chez une population à risque et 3) investiguer si un lien est présent entre le fonctionnement en mémoire de source et la symptomatologie sous-clinique chez une population à risque, à l’instar de ce qui est documenté chez les patients. Les résultats de la thèse ont permis de démontrer que les HRG présentent une atteinte de la mémoire de source ciblée à l’attribution du contexte temporel des souvenirs, ainsi que des distorsions mnésiques qui se manifestent par une fragmentation des souvenirs et par une défaillance de la métacognition en mémoire. Il a également été observé que les expériences hallucinatoires sous-cliniques étaient plus fréquentes chez les HRG. Des associations ont été documentées entre certaines distorsions en mémoire et la propension à halluciner. Ces résultats permettent d’identifier de nouveaux indicateurs cliniques et cognitifs du risque de développer une psychose et permettent de soulever des hypothèses liant l’attribution de la source interne-externe de l’information et le développement de la maladie. Les implications empiriques, théoriques, méthodologiques et cliniques de la thèse sont discutées.

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.

Estudo Comparado entre Alcoólicos e Não Alcoólicos: sintomas psicopatológicos: amostra brasileira

Os sintomas psicológicos nos indivíduos consumidores de álcool é o tema investigado neste trabalho, que se dedicou a analisar as diferenças entre grupos de indivíduos alcoólicos e não alcoólicos homens e mulheres. A oportunidade desta investigação se originou no trabalho de psicologia clínica com pacientes alcoólicos e, principalmente, frente às carências bibliográficas no mercado sobre o assunto. O presente trabalho, buscou, portanto, investigar-se, a partir das hipóteses, a intensidade de problemas psicológicos e sintomas psicopatológicos em sujeitos alcoólicos de ambos os sexos. Para tal, foram realizadas entrevistas orientadas para a aplicação do instrumento. O instrumento utilizado na pesquisa foi o SCL 90-R (Symptom Check List 90 - Revised) (DEROGATIS, 1983) que se propõe a medir a intensidade dos sintomas, especificamente em casos de alcoolismo, sendo este instrumento validado no Brasil (LALONI, 2001). Os sintomas psicológicos avaliados foram: Psicose, Relações Interpessoais, Ansiedade, Ideação Paranóide, Hostilidade, Depressão, Fobia e Obsessivo Compulsivo. A população investigada abrangeu pessoas não consumidoras de álcool da comunidade e pessoas alcoólicas pertencentes aos AA (Alcoólicos Anônimos). Os dois grupos pertencem à Região Metropolitana de Porto Alegre no Estado do Rio Grande do Sul, Brasil. A comparação foi abrangente em relação aos aspectos de gênero, pois além de comparar o grupo de alcoólicos e não alcoólicos verificou as relações de gênero, analisando as diferenças entre o grupo de homens e mulheres alcoólicos e não alcoólicos. Os resultados encontrados demonstram que os alcoólicos são mais sintomáticos que os não alcoólicos e as mulheres apresentam-se em relação aos sintomas avaliados com médias mais altas que os homens. Os alcoólicos homens e mulheres não diferem de forma estatisticamente significativa em seus sintomas psicológicos. Da mesma forma homens e mulheres não alcoólicos não diferem em seus sintomas psicológicos. / The subject of this research concerns about psychological symptoms on alcohol consuming individuals, analyzing the differences between groups of alcoholic and non alcoholic individuals, men and women. This investigation arose from the psychological clinic work with alcoholic patients in face of the lack of literature about this subject. Based on the hypothesis we investigated the intensity of psychological problems and psychopathological symptoms in alcoholic individuals of both sexes. We also evaluated the presence and intensity of psychological problems and psychopathological symptoms in non alcoholic individuals of both sexes. For this research we performed interviews oriented to the application of the instrument. The instrument employed in the research was SCL 90-R (Symptom Check List 90 - Revised) (DEROGATIS, 1983) which measures the intensity of the symptoms. The instrument was validated in Brazil (LALONI, 2001) and is specific to evaluate symptoms in case of alcoholism. The psychological symptoms we evaluated were: Psychosis, Interpersonal Relations, Anxiety, Paranoid Ideation, Hostility, Depression, Phobia, and Obsessive Compulsive. The population investigated is formed by non alcohol consuming people and alcoholics belonging to the Anonymous Alcoholics (AA). Both groups are from the Metropolitan Region of Porto Alegre in the southern sate of Rio Grande do Sul, Brazil. The comparison was comprehensive regarding the aspects of gender, since besides comparing the group of alcoholics and non alcoholics, it compared alcoholic men and women among themselves, and non alcoholic men and women as well. The results that were found demonstrate that alcoholics are more symptomatic than non alcoholics and women, regarding the evaluated symptoms, present themselves with higher averages than men. Alcoholic men and women do not expressively differ in their psychological symptoms, as non alcoholic men and women do not expressively differ in their psychological symptoms as well.

The ins of the striatum: Utilizing chemogenetics to define the contribution of cortical and thalamic afferents during addiction behaviors

Thesis (Ph.D.)--University of Washington, 2016-08

Deteção da simulação em indivíduos com e sem diagnóstico de depressão

A simulação consiste na produção voluntária de sintomas físicos e psicológicos para obter compensações externas. O presente estudo tem como objetivo avaliar a eficácia de um conjunto de instrumentos utilizados na identificação de situações de simulação, bem como averiguar se esses instrumentos são sensíveis a sintomas psicopatológicos. Deste modo, espera-se que os resultados obtidos pelos grupos com depressão e sem depressão honestos difiram significativamente dos resultados obtidos pelo grupo sem depressão simulador. Para tal, foi recolhida uma amostra de 59 sujeitos, todos do sexo feminino, divididos por três grupos: com diagnóstico de depressão (n=19), sem diagnóstico de depressão simuladores (n=20) e sem diagnóstico de depressão honestos (n=20). O protocolo de avaliação incluiu o Test of Memory Malingering (TOMM: Tombaugh, 1996), o Structured Inventory Malingered Symptomatology (SIMS: Widows & Smith), os subtestes de Memória de Dígitos e dos Cubos da WAIS-III, (Wechsler, 1997) e a Figura Complexa de Rey (FCR: Rey, 1988). Os resultados não sugerem diferenças significativas no primeiro e segundo ensaios de aprendizagem do TOMM entre os grupos em estudo. No ensaio de retenção, o grupo sem diagnóstico de depressão simulador difere significativamente do grupo sem diagnóstico de depressão honesto. No SIMS, apenas a subescala Psicose (P) difere significativamente entre os grupos com diagnóstico de depressão e sem diagnóstico de depressão simulador. As subescalas Défices Neurológicos (NI), Perturbações Afetivas (AF), P e Perturbações Mnésicas (AM), com exceção da escala Capacidade Intelectual Reduzida (LI) diferem significativamente entre os grupos com diagnóstico de depressão e sem diagnóstico de depressão honesto e entre este e o grupo sem diagnóstico de depressão simulador. No subteste de Memória de Dígitos verifica-se diferenças significativas entre os grupos sem diagnóstico de depressão simulador e honesto. No subteste dos Cubos não foram encontradas diferenças significativas entre os grupos estudados e na cópia da FCR foram encontradas diferenças significativas entre os grupos com diagnóstico de depressão e sem diagnóstico de depressão simulador. Este estudo contribui para o enriquecimento da literatura nacional e internacional, uma vez que inclui um grupo clínico e alguns instrumentos que não são habitualmente utilizados numa avaliação de simulação. Para além disso, estes resultados têm implicações no contexto clínico e forense, no sentido preventivo e de conhecimento da doença mental.

Identifying Risk Factors for Postpartum Mood Episodes in Bipolar Disorder – A UK Prospective Study

Background and Aims: Women with bipolar disorder are vulnerable to episodes postpartum, but risk factors are poorly understood. We are exploring risk factors for postpartum mood episodes in women with bipolar disorder using a prospective longitudinal design. Methods: Pregnant women with lifetime DSM-IV bipolar disorder are being recruited into the Bipolar Disorder Research Network (www.BDRN.org). Baseline assessments during late pregnancy include lifetime psychopathology and potential risk factors for perinatal episodes such as medication use, sleep, obstetric factors, and psychosocial factors. Blood samples are taken for genetic analysis. Perinatal psychopathology is assessed via follow-up interview at 12-weeks postpartum. Interview data are supplemented by clinician questionnaires and case-note review. Potential risk factors will be compared between women who experience perinatal episodes and those who remain well. Results: 80 participants have been recruited to date. 32/61 (52%) women had a perinatal recurrence by follow-up. 16 (26%) had onset in pregnancy. 21 (34%) had postpartum onset, 19 (90%) within 6-weeks of delivery: 11 (18%) postpartum psychosis, 5 (8%) postpartum hypomania, 5 (8%) postpartum depression. Postpartum relapse was more frequent in women with bipolar-I than bipolar-II disorder (45% vs 17%). 62% women with postpartum relapse took prophylactic medication peripartum and almost all received care from secondary psychiatric services (95%). Conclusions: Rate of postpartum relapse is high, despite most women receiving specialist care and medication perinatally. A larger sample size will allow us to examine potential risk factors for postpartum episodes, which will assist in providing accurate and personalised advice to women with bipolar disorder who are considering pregnancy.

Autistic and Schizotypal Traits and Global Functioning in Bipolar Disorder

Background and Aims To determine the expression of autistic and positive schizotypal traits in a large sample of adults with bipolar disorder (BD), and the effect of co-occurring autistic and positive schizotypal traits on global functioning in BD. Methods Autistic and positive schizotypal traits were assessed in 797 individuals with BD recruited by the Bipolar Disorder Research Network (BDRN), using the Autism-Spectrum Quotient and Kings Schizotypy Questionnaire (KSQ), respectively. Differences in global functioning (rated using the Global Assessment Scale) during lifetime worst depressive and manic episodes (GASD and GASM respectively) were calculated in groups with high/low autistic and positive schizotypal traits. Regression analyses assessed the interactive effect of autistic and positive schizotypal traits on global functioning. Results 47.2% (CI = 43.7–50.7%) showed clinically significant levels of autistic traits. Mean of sample on the KSQ-Positive scale was 11.98 (95% CI: 11.33–12.62). In the worst episode of mania, the high autistic, high positive schizotypal group had better global functioning than the low autistic, low positive schizotypal group (mean difference = 3.72, p = 0.004). High levels of co-occurring traits were associated with better global functioning in both mood states in individuals with a history of psychosis (GASM: p < 0.001; GASD: p = 0.055). Conclusions Expression of autistic and schizotypal traits in adults with BD is prevalent, and may be important to predict course of illness, prognosis, and in devising individualised therapies. Future work should focus on replicating these findings in independent samples, and on the biological and/or psychosocial mechanisms underlying better global functioning in those who have high levels of both autistic and positive schizotypal traits.

Lo que sé de los hombrecillos de Juan José Millás: la ficción psicótica de la sociedad perfecta.

This short essay deals with literary representations of identity and of social reality, especially in relation to the novelistic works published by the Spanish writer Juan José Millás. The article is divided into three parts. The first section is dedicated to a general overview of the new perspectives brought by the contemporary ‘linguistic turn’ in culture, which is currently considered as the product of different discourses and not as an ontological datum. The postmodern condition, on the other hand, is described as the age in which it has become radically difficult to rely on such ideas as “nation” and “people” for the construction of personal identity. The second part of the article identifies Millás’ poetics as an excellent example of describing the neurotic symptoms produced by the urban way of life in Western communities. Millás recognizes the separateness between language and material reality as the origin of the subject's isolation, especially in contemporary life. Finally, the third part handles with Lo que sé de los hombrecillos, the last novel by Millás, in which we witness a significant switch from neurosis to psychosis in the mind of the protagonist who offers us a distorted realisation of his idea of community and plenitude.

The analysis and detection of new psychoactive substances in biological matrices

New psychoactive substances (NPSs) have appeared on the recreational drug market at an unprecedented rate in recent years. Many are not new drugs but failed products of the pharmaceutical industry. The speed and variety of drugs entering the market poses a new complex challenge for the forensic toxicology community. The detection of these substances in biological matrices can be difficult as the exact compounds of interest may not be known. Many NPS are sold under the same brand name and therefore users themselves may not know what substances they have ingested. The majority of analytical methods for the detection of NPSs tend to focus on a specific class of compounds rather than a wide variety. In response to this, a robust and sensitive method was developed for the analysis of various NPS by solid phase extraction (SPE) with gas chromatography mass spectrometry (GCMS). Sample preparation and derivatisation were optimised testing a range of SPE cartridges and derivatising agents, as well as derivatisation incubation time and temperature. The final gas chromatography mass spectrometry method was validated in accordance with SWGTOX 2013 guidelines over a wide concentration range for both blood and urine for 23 and 25 analytes respectively. This included the validation of 8 NBOMe compounds in blood and 10 NBOMe compounds in urine. This GC-MS method was then applied to 8 authentic samples with concentrations compared to those originally identified by NMS laboratories. The rapid influx of NPSs has resulted in the re-analysis of samples and thus, the stability of these substances is crucial information. The stability of mephedrone was investigated, examining the effect that storage temperatures and preservatives had on analyte stability daily for 1 week and then weekly for 10 weeks. Several laboratories identified NPSs use through the cross-reactivity of these substances with existing screening protocols such as ELISA. The application of Immunalysis ketamine, methamphetamine and amphetamine ELISA kits for the detection of NPS was evaluated. The aim of this work was to determine if any cross-reactivity from NPS substances was observed, and to determine whether these existing kits would identify NPS use within biological samples. The cross- reactivity of methoxetamine, 3-MeO-PCE and 3-MeO-PCP for different commercially point of care test (POCT) was also assessed for urine. One of the newest groups of compounds to appear on the NPS market is the NBOMe series. These drugs pose a serious threat to public health due to their high potency, with fatalities already reported in the literature. These compounds are falsely marketed as LSD which increases the chance of adverse effects due to the potency differences between these 2 substances. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was validated in accordance with SWGTOX 2013 guidelines for the detection for 25B, 25C and 25I-NBOMe in urine and hair. Long-Evans rats were administered 25B-, 25C- and 25I-NBOMe at doses ranging from 30-300 µg/kg over a period of 10 days. Tail flick tests were then carried out on the rats in order to determine whether any analgesic effects were observed as a result of dosing. Rats were also shaved prior to their first dose and reshaved after the 10-day period. Hair was separated by colour (black and white) and analysed using the validated LC-MS/MS method, assessing the impact hair colour has on the incorporation of these drugs. Urine was collected from the rats, analysed using the validated LC-MS/MS method and screened for potential metabolites using both LC-MS/MS and quadrupole time of flight (QToF) instrumentation.