Rozprawy doktorskie na temat „Disorder system”

Wireless Sensor Networks  (WSNs) are essential technologies for environmental monitoring. They are composed of small electronic devices, which can monitor, collect and report  environmental data autonomously and continuously with respect to energy consumption and accuracy of data. Recently, mobile phones have become integral part of our daily lives. They have been widely used as mobile sensors to monitor the human behaviour and emotion. Mental problem is becoming a global concern in modern society. Some of the psychological problems, such as Seasonal Affective Disorder (SAD), may cause depression and sickness due to the lack of sunlight in long and dark winters. In this master thesis, we design a system, named Seasonal Affective Disorder Monitoring (SADM), to measure human sociability and light exposure to study the SAD psychological problem among people. The goal of this work is to monitor and improve the mental and physical health of people in our society. The system utilizes both stationary sensors and mobile sensors for monitoring light intensity and human activities continuously, which can help us to learn more about their mental and physical health in diff( erent seasons. The results give us a history of the level of the people's activity and also the percentage of light intensity in the environment and light intensity that individuals received in daily life. Using this information, we analyse the relation between human behaviour and seasonal changes.

Attention Deficit/Hyperactivity Disorder has garnered controversy in the United States since it became a widely diagnosed disorder in American schoolchildren in the 1970s. Both diagnosis and treatment are sites of controversy. Some believe the disorder is a contrivance of parents and teachers who do not want to deal with hardly exceptional childhood difficulties, or a contrivance of pharmaceutical companies taking advantage of such parents and teachers. Others believe that a neurobiological basis for the disorder will eventually be discovered, and thus will legitimize both the diagnosis and the practice of prescribing medication for treatment. I utilize the Science, Technology, and Society approach of actor network theory to show that these multiple understandings of ADHD can coexist, since ADHD is a complex product of external and internal agents. This will demonstrate how cultural shifts and values cause parents, teachers, and doctors to evaluate childhood in a way that frames certain behaviors as harmful. I also evaluate how cultural values of medicalization center issues in the individual rather than in external factors, and assess the values that psychiatric treatment appeals to and whether they primarily serve the needs of children. I conclude that ADHD is a heavily context-dependent disorder, but that that does not delegitimize harmful effect on children who exhibit ADHD-associated behaviors. I also conclude that the current dominant medicalized approach to ADHD is not optimal because it focuses on only a few of the total factors that make ADHD a pathological disorder for children in the contemporary United States.

Introduction: Neuromuscular disorders (NMDs) cause wasting and weakening of muscles. People affected by NMDs and their carers can experience a number of adverse psychosocial consequences, which can be exacerbated by the rare nature of many of these disorders. This makes access to medical information, timely diagnoses, supportive care and peer support difficult. Options for receiving peer support are increasing through the development of online support groups (OSGs) for people affected by NMDs. Aims: This thesis examined the role of a new OSG in facilitating online peer support for people affected by NMDs and their carers. This was carried out using two distinct, but inter-related, studies. The first study examined the various ways in which members used the message board facility. The second of these studies accessed members’ personal experiences of using this OSG. Methods: In order to examine how members used this new OSG, the first study involved an inductive thematic analysis of OSG message postings. Message postings from the first five months of this OSG’s existence (n=1,914) were analysed, so as to identify the main thematic content of members’ discussions. The second study accessed participants’ personal accounts of their OSG experiences. Semi-structured interviews were conducted with six OSG members and were analysed using Interpretative Phenomenological Analysis (IPA). This interview element examined the context through which members decided to use the group, factors that contributed to their continued use of the group, and the personal impact of participation. Results: The OSG message postings analysis demonstrated how members created a sense of community spirit by establishing common ground through disclosing personal information, searching for connections with people with similar illness experiences or interests, welcoming new members, and sharing aspirations for the development of a resourceful community. Experiences, emotional reactions and support were shared in relation to: delayed diagnosis; symptom interpretation; illness management and progression; and the sense of isolation incurred when managing a rare disorder. The board was also used to discuss societal and political issues pertaining to living with an NMD and methods of raising awareness of such conditions. The results of the interview study showed the valued connection that the OSG gave participants to similar others, in a friendly, non-pressurised environment. Members especially valued the reassurance of knowing that they were not alone in coping with their often-rare condition. The group provided participants with an understanding audience: a rare experience for a group whose condition is not widely known or understood. The information exchanged on the OSG was appreciated due to its specificity in dealing with NMDs. The board was also considered an important platform for raising awareness of NMD-related issues. The gratifying experience of helping other NMD sufferers was highlighted as a key theme. Participants also felt that the OSG was not without its limitations. Difficulties in relating to other people (because of varying disability levels, different disease progression histories, and different views on politics and other interests) influenced participants’ levels of interaction and the perceived benefits of the group. Less common concerns for the group – but important for some individuals – were privacy concerns in using a publicly accessible group and difficulty navigating through the message postings. Conclusions: This thesis provides a novel, in-depth insight into how people used a new OSG for NMDs, and the personal impact of participating in such a group. Analyses of message posting and interview data highlight the vital psychosocial support provided by the OSG, especially given the rarity of many of these conditions. However, it was found that some obstacles to support are inherent in the OSG itself, tempering assessments of the impact of its use.

The profile of caregivers to Alzheizner’s disease victims in Georgia was examined. The sample population consisted of 377 caregivers (20% of the registered members of the 16 Alzheimer’s Support Groups across the state). The findings revealed that, the majority of the caregivers are between the ages of 45 and 74 years old, they tend to be the spouse of the victim, live on a fixed income, and is experiencing emotional, physical and financial stress. The findings were analyzed utilizing tables and percent comparisons.

The study aimed to test how progress on achievement and power goals, and perceptions of power, fluctuate with mania symptoms in Bipolar Disorder (BD), testing the Dominance Behavioural System (DBS) model. The DBS includes biological, psychological, and behavioural components that serve the goal of control over social and material resources needed for survival and reproduction (Johnson, Leedom, & Muhtadie, 2012c). Daily diary methodology was employed, with 29 individuals meeting the Diagnostic and Statistical Manual-Fourth Edition (DSM-IV) criteria for BD I or II as verified by the Structured Clinical Interview [SCID-I-RV] (First, Spitzer, Gibbon & Williams, 2002). Baseline measures of dominance motivation and ambitious goal setting were taken. Over fourteen days, participants reported daily on their goal progress, symptoms of mania, power, and anger. It was hypothesised there would be a positive relationship between symptoms of mania and dominance motivation. It was also hypothesised that for power but not achievement goals, ii) goal progress would be associated with perceptions of power, iii) symptoms of mania, and iv) that goal frustration would be associated with anger. Pearson’s correlations and multilevel modelling analyses found largely null results with the exception of a positive relationship between progress towards power goals and perceptions of power. Thus, the results did not provide support for the DBS model predictions for relationships between power goals and manic symptoms. Future studies could utilise further measures of dominance motivation and power, and study goal pursuit over a more protracted duration, including comparisons between BD, depressed groups, and healthy controls.

The discovery of mirror neurons and the mirror neuron system is one of the most interesting breakthroughs in the field of neuroscience in recent years. The topic stretches over a wide spectrum of research fields but one of the more prominent areas is concerned with the role of mirror neurons in autism spectrum disorder. It is hypothesized that an impaired mirror neuron system may be one of the main causes underlying the deficits seen in autistic individuals. Parallel to the broken mirror theory of autism there are critical voices claiming there is not enough empirical evidence to support such a theory. Research carried out in the area seems to offer support for both contradictory approaches making it hard to conclude the definite role of mirror neurons in this developmental disorder. Future research may offer conclusive answers concerning the role of the mirror neuron system in autism spectrum disorder as well as other important questions regarding the functional properties of the brain areas under question.

There is evidence that dopaminergic dysfunction plays a role in the symptoms of bipolar disorder although the precise abnormality is unclear. In addition clysregulation of corticosteroid secretion characterised by a flattened diurnal circadian rhythm has been observed across mood states in bipolar disorder. As a result it has been hypothesised that corticosteroid hypersecretion underlies the dopaminergic dysfunction. Here the endocrine regulation of mesocorticolimbic doparninergic neurotransmission was investigated with the hope of bettering our understanding of the pathology of bipolar disorder. Immunocytochemical studies established that around half of dopaminergic neurones in the ventral tegmental area (VTA) express the low affinity glucocorticoid receptor (GR), whilst all of these neurones express the high affinity mineralocorticoid receptor (MR). This indicated that corticosteroids can directly modulate dopaminergic neuronal function. By administering corticosterone to rats in their drinking water a flattened circadian profile of corticosteroid secretion similar to that seen in bipolar disorder was modelled. In situ hybridisation histochemistry in the VTA revealed that corticosterone treatment increased the transcription of mRNA for tyrosine hydroxylase, the vesicular monoamine transporter and the D2 receptor, whilst decreasing expression of the 5-HT2c receptor and the GluRl subunit of the AMPA receptor. In vivo microdialysis in the medial prefrontal cortex demonstrated increased doparnine release under both basal and stimulated conditions in corticosterone treated animals. This effect did not appear to be the result of altered D2 autoreceptor function or a change in the firing rate of cloparninergic neurones. In light of the in situ hybridisation data it is hypothesised that flattening the diurnal profile of corticosteroid secretion increases prefronto-cortical doparnine release by upregulating dopamine synthesis and vesicular uptake. These studies demonstrate that corticosteroid dysrhythmia of the type seen in bipolar disorder can alter doparninergic neurotransmission and furthermore they indicate specific aspects of dopaminergic function which might be altered. Thus circadian rhythm abnormalities in the HPA axis may play a role in the aetiology of bipolar disorder via clysregulation of dopaminergic neurotransmission.

Background: Central Nervous System (CNS) inflammatory syndromes represent a spectrum of diseases caused by infiltration of inflammatory cells into the tissue of the brain and spinal cord. They comprise a group of diseases that can be acute or chronic, including optic neuritis, transverse myelitis, acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO) and its spectrum disorders (NMOSD), clinically isolated syndrome (CIS) and multiple sclerosis (MS). MS is the most common one while NMO/NMOSD is relatively rare although the exact population-based epidemiological parameters are lacking. The distinction of MS and NMO/NMOSD in adult patients and of MS and ADEM in paediatric patients is important for considerations of prognosis and treatment. This thesis aims to differentiate NMO/NMOSD from MS using epidemiology analyses and quantitative magnetic resonance imaging at 7 Tesla. The hypothesis of the thesis is that NMO/NMOSD can be differentiated from MS by disease incidence, prevalence, severity, and the quantitative characteristics of the lesion and non-lesion white matter of the brain. Methods: The thesis firstly employed a comparative epidemiological study to estimate incidence and prevalence of MS and NMO/NMOSD, and to estimate risks for associated comorbidities and mortality between NMO/NMOSD and MS. The thesis then applied two quantitative techniques to compare the white matter lesions and non-lesion white matter (so-called normal-appearing white matter [NAWM]) of both NMO/NMOSD and MS. Results: The results are presented in seven chapters. Chapter 1 provides a general review of CNS inflammatory syndromes. Chapter 2 shows the estimated incidence and prevalence of CNS inflammatory diseases in 2012 using the Clinical Practice Research Datalink (CPRD). MS is estimated to be the most prevalent and the NMO/NMOSD the rarest. Chapter 3 shows the case-controlled analytic results on the impact of the burden of comorbidity in MS. The burden is cumulative after MS diagnosis and impacts on patient survival compared to non-MS patients. With an interest of new-onset epilepsy in the course of MS compared to non-MS controls, chapter 4 shows that MS patients have a higher risk of having the first medical recorded epilepsy at and after MS diagnosis. Chapter 5 shows the comorbidity burden in NMO/NMOSD, and estimates the risk for mortality between NMO/NMOSD and age- and gender-matched MS populations. Chapter 6 compares in vivo white matter lesions and NAWM of the brain between adult patients with NMO/NMOSD or MS and healthy subjects using quantitative T1 relaxation time and magnetisation transfer ratio (MTR) magnetic resonance imaging at 7 Tesla. The results show that myelin content of white matter lesions is relatively better-preserved in NMO/NMOSD than that in MS; and they also show some changes in the NAWM of NMO/NMOSD, despite the fact that the metrics of the histogram of both sequences are not different to those in MS. Conclusions: In the UK, NMO/NMOSD is rare with a higher disease severity compared to MS, which is the most prevalent inflammatory disease. In vivo, using T1 relaxation time and MTR imaging at 7 Tesla, the white matter lesions of the brain have more preserved myelin in patients with NMO/NMOSD than in those with MS. There is at least a small proportion of intracranial NAWM having subtle changes in patients with NMO/NMOSD that is detectable, but the changes could not be differentiated from MS in the current study. This thesis helps to better understand the epidemiology of NMO/NMOSD and MS, and MRI detectable changes of lesions and NAWM in NMO/NMOSD.

Performance-related musculoskeletal disorders in musicians are common due to the biomechanics required in their craft. Unfortunately, injuries can cause many to abandon music, so determining the best approach to treatment and prevention is key. This case study’s importance is to evaluate the optimal approach to carpal tunnel syndrome in a drummer. The patient is a 55-year-old male full-time drummer with a history of diabetes mellitus and osteoarthritis, who presented to clinic with chronic bilateral hand numbness and tingling that had been present for years. The location of the symptoms were mainly in the palmar aspect of the 1st digit, 2nd digit, 3rd digit, and the radial side of the 4th digit. The symptoms had progressively been worsening, and his discomfort was initially rated at a 10/10 bilaterally. He had tried over-the-counter and prescription anti-inflammatory medications as well as braces without improvement. His physical exam was positive for Tinel’s sign. The diagnosis of carpal tunnel syndrome was eventually made. The patient was treated with bilateral ultrasound-guided carpal tunnel injections with lidocaine and methylprednisolone. The other component of treatment was relative rest, which allowed us to tailor treatment to his drumming. After treatment, his discomfort was rated at 0/10 bilaterally, and he was drumming without issue. It was found that relative rest and carpal tunnel injections are effective in treating carpal tunnel syndrome in drummers. His treatment was tailored to his specific instrument type, which was a key component to the success. Upon review, there is limited to no specific information on treating drummers as a specific group in the literature, but rather more information on treating musicians as a whole. Different instrumentalists have different postures and repetitive movements, so future studies would do well to examine the individual biomechanics of the different instrumentalists to better tailor treatment and prevention.

The purpose of this study was to discover the current awareness of speech-language pathologists (SLPs) regarding the link between language disorder and the juvenile justice system. It is to consider how speech-language pathology, as a profession, think about the implications of language disorder on life outcomes as well as determine the need for speech-language intervention within the juvenile justice system. A Google Form was created and distributed to current speech-language pathologists that have their Certificate of Clinical competence, and have experience working with students in the educational setting. Results suggest SLPs are aware of the link between LD and the juvenile justice system as well as the aspects of language found difficult for these young offenders, but training and professional development on this topic is minimal. Participants report an interest in interprofessional practice and are positioned to become advocates for young offenders with LD in the juvenile justice system.

The purpose of the current study was to evaluate the effectiveness of whether Behavioral Skills Training (BST) was effective in teaching PEAK-DT to parents of children with Autism Spectrum Disorder (ASD). Along with, if parent implementation of PEAK was effective in increasing the children’s PEAK scores. Three parents and their child with autism were participants in the current study using the PEAK Relational Training System-Direct Training module (PEAK-DT). The procedure first required the parents to read information on how to implement the programs found in the introduction of the PEAK-DT module. Following this step, parents observed their child’s therapy sessions conducted at an ABA clinic by student therapists. Next, the parents were instructed to implement three programs and received feedback from the child’s therapist. Implementation fidelity was collected based on the parent performance and child progress was recorded based on percent correct responding within the actual program. Each parent was able to successfully implement programs within the PEAK-DT module within their child’s therapy sessions and the children were accurately responding and two of the three children had increases in skill acquisition. The results of the present study suggest that training parents using a BST model to implement PEAK-DT was effective in teaching children with autism.

The primary purpose of this study was to identify the information and to develop a prototype expert system to assist in the assessment of specific psychological disorders that may be directly or indirectly the cause of some learning disabilities. This tool will assist teachers as well as parents in recognizing the symptoms of a possible disorder, in identifying the tests that are available to confirm the existence of the disorder, and in minimizing the effects of the disorder to the greatest extent possible through early diagnosis and intervention. In order to develop a prototype expert system this study was limited to Dyslexia and Attention Deficit Hyperactivity Disorder (ADHD). The prototype was developed with the assistance of Psychiatrist and Psychologists. The prototype was field tested with ninety five percent correct diagnoses.

Psychology
Ph.D.
Although the current literature demonstrates relations between autonomic nervous system (ANS) functioning and conduct disorder (CD), there are inconsistencies across studies in the magnitude and direction of these associations, some of which may stem from heterogeneity within the CD diagnostic category. Considering callous-unemotional (CU) traits in research examining ANS functioning and CD relations could help to clarify these inconsistencies, given that CU traits identify a subgroup of youth with CD who exhibit a more severe and persistent course, as well as more negative correlates and sequelae than youth with CD without CU traits. However, there is a dearth of literature considering ANS processes among youth with CD with and without CU traits. Examining these relations, particularly during middle childhood when these processes may be amenable to intervention, has important implications for etiological, prevention, and intervention models. The present study examined relations among CD, CU, and ANS functioning among a sample of ethnic minority, urban children (N= 99, M= 9.87± 1.19 years old; 48.5% male; 94.9% African-American, 3% Latino/a). Specifically, I examined whether CU traits moderated the relations between CD and (a) parasympathetic nervous system (PNS) functioning and (b) sympathetic nervous system (SNS) functioning. In addition, I examined whether parenting behaviors (i.e., harsh parental discipline and parental warmth/involvement) influenced the relations between (a) CD and ANS functioning, and (b) CU and ANS functioning. Findings demonstrated that PNS functioning differed among children with high and low levels of CD symptoms depending on levels of CU traits. Within the current sample, among children with higher levels of CD symptoms, those with (a) higher CU symptom severity exhibited lower baseline respiratory sinus arrhythmia (RSA) and lower RSA reactivity (PNS withdrawal), compared to those with (b) lower CU symptom severity who demonstrated higher baseline RSA and higher RSA reactivity (PNS activation). Among children with lower CD symptom severity, those with (a) higher CU symptom severity exhibited higher baseline RSA and higher RSA reactivity, compared to those with (b) lower CU symptom severity who evidenced lower baseline RSA and lower RSA reactivity. Neither harsh parental discipline nor parental warmth/involvement moderated the relations between (a) CD and ANS functioning and (b) CU and ANS functioning. However, there were marginally significant associations between baseline RSA and (a) harsh parental discipline and (b) parental warmth/involvement, as well as between RSA reactivity and parental warmth/involvement in analyses examining CD, parenting, and ANS functioning. Furthermore, parental warmth/involvement tended to be associated with RSA reactivity in the analyses examining CU, parenting, and ANS functioning. Results have implications for facilitating the identification of children at risk for developing more pernicious subtypes of behavior problems, and contribute important information for the development of more individualized and potentially effective interventions for youth behavior problems, particularly among high-risk youth.
Temple University--Theses

Interview strategies applied in adult criminal justice settings focus on the interviewer and concentrate on obtaining information for the courts, while simultaneously neglecting a forensic understanding of interviewees, including the interviewee's decision-making and behavioral health impairments. As a consequence, there is a deficiency of evidence-based research regarding interview practices with persons diagnosed with antisocial personality disorder (ASPD). Using social control and neutralization theories as the foundation, the purpose of this case study of a single justice system in the United States was to better understand the perspectives and experiences of ASPD diagnosed inmates (n =5) compared to incarcerated participants without any mental health diagnosis (n =5) regarding willingness to cooperate with the interviewer. Interview data were triangulated with the Gudjonsson Confession Questionnaire – Revised. Data were inductively coded and then subjected to a thematic analysis procedure. Results indicate that external and internal pressures, intoxication, perception of proof, involvement of third parties, and/or a lack of insight into diagnostic features of ASPD influenced decisions to cooperate with an interviewer, thereby impacting the quality of interview results. The positive social change implications of this study include recommendations to criminal justice systems to explore holistic interview strategies that may improve interview outcomes. Adhering to this recommendation may improve the quality of interviews and ensure that justice system objectives related to truthfulness and accuracy are enhanced as well as improve mental health outcomes of criminal offenders.

Thesis (M.A.)--Kent State University, 2008.
Title from PDF t.p. (viewed Oct. 15, 2009). Advisor: Joel Hughes. Keywords: PTSD, autonomic nervous system, parasympathetic nervous system, heart rate variability. Includes bibliographical references (p. 45-57).

Thesis (Ph. D. in Speech and Hearing Bioscience and Technology)--Harvard-MIT Program in Health Sciences and Technology, 2012.
Cataloged from PDF version of thesis. Vita.
Includes bibliographical references (p. 78-85).
While evidence from clinical and functional neuroimaging domains converges on a notion that auditory-motor networks can be remodeled functionally and structurally in response to experiences, studies that seek to evaluate these hypotheses by combining behavioral, functional, and structural measures are rare. Given relatively recent advances in neuroimaging, e.g. diffusion-tensor imaging (DTI) and functional neuroimaging methods (fMRI), it is now possible to structurally and functionally analyze these networks, as well as make inferences about them in situations where the networks are either functionally compromised by an auditory-motor feedback disorder, or structurally enhanced by an intense long-term auditory-motor training regimen. To this end, a three-fold course of study has been undertaken: (1) a between-group comparison of the structural aspects of the arcuate fasciculus (a prominent white-matter fiber tract that reciprocally connects the temporal and inferior frontal lobes and is thought to be important for auditory-motor interactions) of singers and those of matched nonsinging musicians, in order to evaluate the hypothesis that singers will exhibit structural differences specifically for aspects of vocal output that require rapid temporal processing and precise sound-motor matching. (2) a within-subject fMRI comparison of responses of young adults (non-musicians) to auditory feedback that is either unperturbed or shifted in pitch while they perform a pitch-matching task, to ascertain a functional network related to perceiving and perhaps compensating for mismatched auditory feedback. (3) a within-subject pilot study of the network ascertained in (2), now in a smaller group of young adults with an auditory-motor disorder/disconnection syndrome commonly referred to as tonedeafness (TD) or congential amusia (a conditioned marked by a high pitch discrimination threshold as well as readily apparent difficulty in matching pitches), in order to provide insight into how this network might behave in a state of long-term disorder. While this work corroborates previous work in clinical, behavioral, and neuroimaging domains, and sheds light on the organization of these auditory-motor networks (structurally and functionally) in the normal population, it also aids in understanding how these networks may be remodeled and optimized (structurally) in response to intense long-term training, how they adapt to an acutely compromised state (i.e. when input to the network is compromised or perturbed), as well as how they may adapt functionally in a chronically compromised state (i.e. tonedeafness). Taken together, these observations help to explain the functioning of the auditory-motor network in normal individuals and those with communication disorders, as well as well as shedding light on possible mechanisms of recovery as they participate in an intensive long-term auditory-motor therapy program.
by Gus F. Halwani.
Ph.D.in Speech and Hearing Bioscience and Technology

Thesis (PhD)--Stellenbosch University, 2008.
ENGLISH ABSTRACT: Investigations into the neurobiology of obsessive-compulsive disorder (OCD) have provided useful insights into this prevalent and disabling disorder in recent decades. Encouraging advances have also been made in the pharmacological treatment of OCD. This has improved the quality of life for many who typically endure chronic unremitting symptoms. Despite the widespread use of first-line agents selective for the serotonergic system in OCD, relatively little is known about the neurobiology of treatment response, the specific components of the serotonin system involved in symptom modulation, and the overlapping and distinct brain regions impacted by alternative treatment options. Despite the advance that selective serotonin re-uptake inhibitors have been, a significant proportion of patients still fail to respond adequately to these agents, and alternative pharmacological interventions are required. The use of dopamine antagonists, a strategy which until recently has had only limited supporting data, presents one such alternative. Little however, is known about which subsets of patients are most likely to respond to these agents. In this thesis, I will present a series of six studies that use pharmacological treatments and single photon emission computed tomography (SPECT) to make contributions to three primary areas in OCD namely; neurobiology, treatment and the intersection of the two. First, I address OCD neurobiology by examining the impact of OCD on resting brain function. I then examine the effects of pharmacological challenge of the serotonin 1B receptor using sumatriptan on regional cerebral blood flow (rCBF) and clinical symptomatology. Second, I examine the intersection of neurobiology and treatment as I explore the changes in rCBF in response to treatment with inositol, a precursor of the phosphoinositol second messenger system. I then examine the distinct and overlapping effects on rCBF of treatment for 12 weeks with the selective serotonin re-uptake inhibitor (SSRI) citalopram across anxiety disorders. Third, I address treatment of OCD by examining the efficacy of controlled augmentation of serotonin re-uptake inhibitors with quetiapine, a dopamine antagonist, in treatment refractory OCD. I then combine this data with a second similar dataset to derive a predictive model for treatment outcome with quetiapine augmentation of SRIs. I demonstrate that rCBF in OCD differs significantly from normal controls, is correlated with severity in frontal brain regions, and remains an important line of investigation for OCD pathophysiology that has yet to fully delineated. Pharmacological challenge of the 5HT1B autoreceptor with the selective agonist sumatriptan results in heterogeneous behavioural and regional brain perfusion changes in OCD. Attenuation of pre-frontal perfusion following 5HT1B agonist administration is in line with the effects of SRIs. This work suggests that direct or indirect effects of SRIs on the 5HT1B receptor may be involved in mediating a clinical response in OCD. In the section exploring the intersection of neurobiology and treatment, I show that changes in rCBF partially parallel treatment response to SSRIs across a range of anxiety disorders. These data suggest that a degree of overlap exists in the neurobiology of treatment response or indeed core neurobiology across different anxiety disorders. I then show that effective treatment with inositol in OCD results in rCBF changes that are partially in line with the effects of SRIs on brain perfusion. These data support suggestions that second messengers may form part of the common pathway of action for effective anti-obsessional compounds. In the study in which we augmented SRIs with quetiapine, no advantage over placebo was found. This data has, however, recently been combined with similar data in meta-analyses and demonstrated a benefit over placebo. Finally, we found that patients who have failed fewer SRI trials, have more severe illness, and clinical dimensions with a putative dopaminergic underpinning, may derive preferential benefit from serotonin/dopamine antagonist augmentation of SRIs. Through this series of clinical treatment and functional brain imaging studies in OCD, I have contributed to the neurobiological understanding of OCD, and its treatment in refractory populations. In addition I have explored the intersection of these two domains using novel as well as conventional treatment across other anxiety disorders. Treatment and pharmacological challenges used, either directly or indirectly impacted the monoamine systems serotonin and dopamine and advanced our understanding of their involvement in symptom generation. Future work should focus on the functional intersection of brain function, treatment response, and functional genetic polymorphisms within the monoamine systems of the brain.
AFRIKAANSE OPSOMMING: Ondersoek na die neurobiologie van obsessief-kompulsiewe steuring (OKS) het in die afgelope dekades sinvolle bydraes gelewer tot die begrip van hierdie algemene en verminkende steuring. Bemoedigende vordering is ook in die farmakologiese behandeling van OKS gemaak. Dit het tot ’n verbetering in kwalitiet van lewe van meeste pasiënte gelei wat normaalweg kronies en onophoudelike simptome moet verduur. Ten spyte van die uiteenlopende gebruik van eerste-linie behandeling wat spesifiek inwerk op die serotonien sisteem in OKS, is relatief min bekend oor die neurobiologie van respons op behandeling. So ook is min bekend oor; eerstens die spesifieke komponente van die serotonien sisteem wat betrokke is by simptoom modulasie, en tweedens die gedeeltelik samevallende en afsonderlike brein streke wat deur alternatiewe farmakologiese behandelings beïnvloed word. Ten spyte van die vooruitgang wat die selektiewe serotonien heropname inhibeerders tot gevolg gehad het, is daar nog altyd ‘n betekenisvolle proporsie van pasiënte wat nie voldoende respondeer op hierdie behandelings opsie nie. Dus word alternatiewe opsies benodig. Een so ‘n opsie is die klas dopamien reseptor blokkeerders wat tot onlangs min ondersteunende data gehad het. So ook, is min bekend oor die subgroepe van pasiënte wat die meeste voordeel uit hierdie alternatief sal trek. In hierdie proefskrif sal ek ‘n reeks van ses studies wat farmakologiese middels en enkel foton emissie rekenaar tomografie (EFERT) gebruik om ‘n bydra tot kennis in drie primêre areas van OKS te maak. By name; neurobiologie, behandeling, en die kruispunt van die twee. Eerstens spreek ek neurobiologie aan deur middel van ’n studie wat rustende brein bloed vloei (rBBV) in OKS ondersoek. Hierna ondersoek ek veranderings op rBBV en simptome na eenmalige toediening van ‘n serotonien 1B reseptor agonis, sumatriptan. Tweedens ondersoek ek die kruispunt van neurobiologie en behandeling deur die effek van behandeling met inositol, ‘n voorloper van die fosfoinositol tweedeboodskapper sisteem, op rBBV. Ek ondersoek dan die rBBV patroon van veranderinge in brein streke wat deur twaalf weke van behandeling met die selektiewe serotonien heropname inhibeerder citalopram in verskeie angversteurings bewerkstellig word. Laastens, spreek ek behandeling van OKS aan deur middel van ‘n gekontroleerde studie wat ondersoek instel na die effektiwiteit van die byvoeging van quetiapien, ‘n dopamien reseptor antagonis, tot serotonien heropname inhibeerders in behandelingsweerstandige OKS. Ek kombineer dan hierdie data met ’n soortgelyke datastel om ‘n model af te lei wat kliniese uitkoms vir hierdie behandelings opsie voorspel. Ek het gedemonstreer dat rBBV in OKS betekenisvol verskil van gesonde vergelykbare kontroles. Hierdie verskille het gekorreleer met ernstigheid van OKS in frontale brein streke. Dus bly hierdie tipe studies ’n belangrike rigting van ondersoek in OKS patofisiologie wat tot op hede nie tenvolle uitgewerk is nie. Eenmalige toediening van sumatriptan, het heterogene gedrags en rBBV veranderings in OKS tot gevolg gehad. Pre-frontale verhogings in rBBV voor behandeling is met 5HT1B sumatriptan toediening verminder, ’n effek wat in lyn staan met die effek van selektiewe serotonien heropname inhibeerders. Hierdie werk stel voor dat direkte of indirekte effekte van selektiewe serotonien heropname inhibeerders op die 5HT1B reseptore betrokke mag wees by die meganisme van behandelingsrespons in OKS. In die afdeling waarin ek die kruispunt van neurobiologie en behandeling ondersoek, demonstreer ek dat rBBV veranderings gedeeltelik oorvleuel met dié wat deur selektiewe serotonien heropname inhibeerders veroorsaak word in verskeie angsversteurings. Hierdie data stel voor dat oorvleueling in die neurbiologie van beide behandelingsrespons en kern neurobiologie van hierdie angversteurings ’n waarskynlikheid is. Ek wys ook dat effektiewe behandeling met inositol in OKS ook veranderings in rBBV bewerkstellig wat gedeeltelik in lyn staan met dié van die selektiewe serotonien heropname inhibeerders. Hierdie data ondersteun dus hipoteses van ‘n gemeenskaplike meganisme, wat tweede boodskapper sisteme insluit, wat in die behandelings respons van effektiewe anti-obsessionale middels betrokke is. Die finale deel van hierdie proefskrif handel oor behandeling van OKS. Ten spyte van die onvermoë om ‘n verskil tussen quetiapien en plasebo te demonstreer, het ons onlangs met hierdie data in ‘n reeks meta-analises wel ‘n voordeel vir hierdie intervensie getoon. Ten slote, het ons gevind dat (1) pasiënte wat minder kursusse selektiewe serotonien heropname inhibeerders gefaal het; (2) voor behandeling ‘n erger vorm van OKS gehad het, en (3) ook voordoen met simptoom dimensies wat oënskynlik ‘n dopaminerge basis het, die grootste waarskynlikheid toon om met quetiapien byvoeging tot selektiewe serotonien heropname inhibeerders te respondeer. Met hierdie reeks behandelings en funksionele breinbeeldings ondersoeke, lewer ek ‘n bydra tot die begrip van OKS. Spesifiek dra ek by tot die begrip van die neurobiologie, hantering van behandelingsweerstandige OKS asook die kruispunt van die twee. Farmakologiese middels wat ons óf eenmalig óf vir ‘n volle behandelingskursus toegedien het, het direkte of indirekte uitwerkings op die serotonien and dopamien sisteme gehad, en dus dra hierdie werk ook by tot kennis oor dié se betrokkenheid al dan nie in simptoom modulasie in OKS. Toekomstige werk in die area sal in die breë fokus op die kruispunt van breinfunksie, behandelingsrespons en funksionele genetiese polimorfismes van die monoamien sisteem.

The biological mechanisms proposed to underlie primary mood disorder do not usually include a neuropathological component. Over recent years, a significant imaging literature attests to structural abnormalities in various brain regions in mood disorder, and has encouraged neuropathological investigations. Although the neuropathological understanding of mood disorder is still rudimentary, structural correlates have begun to emerge. The studies described in this thesis investigate the neuropathology of the anterior cingulate cortex in mood disorder. The anterior cingulate cortex is extremely diverse and complex, particularly in respect to its cytoarchitecture and functional organisation. These details are important when considering the precise localisation and clinical correlates of the neuropathological changes of this region in disease. Accordingly, I performed a detailed analysis of the cytoarchitecture of the human anterior cingulate cortex, as a prelude to investigations of this region in mood disorder. I measured several morphometric parameters within different anatomical levels and both hemispheres of the anterior cingulate cortex. Overall I found a clear distinction in the cellular composition of the supragenual and subgenual regions of the anterior cingulate cortex. The subgenual region demonstrated a lower glial density and smaller neurons in comparison to the supragenual region. A modest difference in neuronal density was also observed, with a higher density in the deep layers of the subgenual cortex compared to the deep layers of the supragenual cortex. Total cortical depth was also thinner in the subgenual region. This work may have important implications for the interpretation of imaging and pathological data in mood disorder. To assess the cytoarchitecture of this brain region in mood disorder, I examined several morphometric indices in addition to various parameters of gene expression in post mortem brains. I found a range of cytoarchitectural abnormalities in the supragenual anterior cingulate cortex in mood disorder. The most prominent change included a reduction in glial density, which was evident in all layers of the cortex. Glial fibrillary acidic protein was also reduced, providing some evidence for astrocyte involvement. Various neuronal changes were also observed in the mood disorder group. These included layer-specific reductions in pyramidal neuron density and a modest change in the density of cairetinin-immunoreactive neurons. I did not find any evidence supporting synaptic pathology in the anterior cingulate cortex in mood disorder. These findings extend previous evidence of cytoarchitectural alterations in the anterior cingulate cortex in mood disorder and in particular emphasise the prominent involvement of glial cells in the neuropathology of this disease. The origins of the glial (and neuronal) deficits in mood disorder remain to be established, but they are likely to have pathophysiological consequences.

MDD is a severe and debilitating disorder that is associated with a growing global economic burden due to reduced workplace productivity along with increased healthcare resource utilization. Furthermore, depression markedly enhances the risk for suicide, mortality that is especially worrisome given that 30% of depressed individuals have an inadequate response to current antidepressants. This inadequacy of antidepressants necessitates the discovery of a better understanding of the pathobiology of MDD. Most current antidepressants work through monoamine neurotransmitters, and their relative efficacy in depression led to the now dated monoamine-deficiency hypothesis. The limited usefulness of antidepressants has led to a reinvigorated search for other pathologies in depression that might yield clues for the development of better drug treatments. In this regard, a strong association has been found between oxidative stress and MDD. Our lab recently found increased DNA oxidation and elevated poly(ADP)ribose polymerase (PARP1) gene expression in the brain from donors that had MDD at the time of death. Besides DNA damage repair, PARP1 mediates several downstream inflammatory effects that may contribute to pathology in MDD. In fact, our lab has demonstrated that PARP-1 inhibition produces antidepressant-like effects in rodents, suggesting that PARP-1 inhibitors hold promise as a novel antidepressant drug. While our lab had previously demonstrated elevated PARP1 gene expression in the frontal cortex in MDD, whether PARP1 protein levels were also increased in depression had not been verified. My thesis research was performed to determine whether PARP1 protein expression was also elevated in the brain in MDD. I studied primarily the hippocampus because it is part of the limbic (mediating emotion) system of the brain and because previous research has shown numerous other pathologies in the hippocampus. My study was carried out simultaneously as others in our lab were measuring PARP1 protein levels in frontal cortex in MDD. This latter work was important since the lab’s previous work had observed elevated PARP1 gene expression in the frontal cortex, rather than in the hippocampus which was not previously studied. Hippocampal and frontal cortical brain sections were cut from frozen blocks of both MDD and psychiatrically normal control brain donors for these studies. PARP1 protein levels were estimated by assisted-imaging software. The findings herein demonstrate that levels of PARP1 immunoreactivity are significantly elevated in the frontal cortex of MDD donors as compared to control donors. However, there was no change in PARP1 immunoreactivity in the hippocampus in MDD.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common disorders of childhood. It is theorized to be caused by catecholamine dysfunction in the striatum (Str) and frontal cortex (FC). The spontaneously hypertensive rat (SHR) has been used as a model for ADHD because of its attention deficits, impulsiveness, and hyperactivity. Prior studies of dopamine (DA) in the Str and FC have revealed conflicting results in the SHR compared to control, indicative of a need for a better understanding of DA dynamics in this model. In addition to the DA hypothesis, studies have begun implicating glutamate in the etiology of ADHD. Previous evaluations of the SHR model of ADHD found that the SHR have increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activity and elevated calcium levels in the FC, suggesting that altered glutamatergic neurotransmission exists in the SHR. The first set of studies presented here suggest that increased surface expression of DA transporters may exist in the SHR model of ADHD, lowering basal DA levels. Second, we discovered that the glutamate system in the FC of the SHR model of ADHD is hyperfunctional, thus raising the possibility that targeting glutamate dysfunction in the FC could lead to the development of novel therapeutics for the treatment of ADHD. The third and fourth set of studies explored glutamate signaling in the awake rodent to fully understand glutamate neurotransmission as well as the effects of methylphenidate (MPH) on glutamate signaling in the prelimbic cortex, a region heavily implicated in ADHD. The SHR displayed similar phasic glutamate signaling compared to control; however, in the SHR but not the WKY control, chronic treatment with MPH lowered phasic glutamate amplitude. Additionally, intermediate treatment with MPH increased tonic glutamate in the SHR only, whereas chronic MPH treatment increased tonic levels in both the SHR and WKY compared to saline. Taken together, this body of work characterizes DA and glutamate signaling in the anesthetized SHR model of ADHD. Additionally, glutamate dynamics and the effects of the stimulant medication MPH were explored in the awake animal, providing evidence that glutamate is a likely target for future neuropharmacology for the treatment of ADHD.

Bipolar disorder is characterized by disruptions in mood and affect that occur not only during mood episodes, but during euthymic periods as well. At the same time, sensitivity of the behavioral activation system (BAS) has been implicated in the disorder and is a risk marker for it. Less clear is the relationship between BAS sensitivity and positive affect, particularly lower level facets of positive affect. The aim of the present study was to examine the relationship between positive affect and vulnerability for mania as assessed using BAS sensitivity. Specifically, the link between daily levels and fluctuations of positive affect and baseline BAS sensitivity was examined. Following the hierarchical model of affect, this study also assessed the relationship between BAS sensitivity and the distinct facets of positive affect. Finally, this study examined whether BAS sensitivity moderates associations between daily rewards and positive affect. Undergraduates (N = 265) from a large university in the South were recruited to complete measures of BAS sensitivity, affect, and mood symptoms at baseline. Using ecological momentary assessment (EMA), participants completed daily surveys assessing affect and engagement with rewarding situations. An exploratory factory analysis revealed a four factor structure of positive affect, consisting of Serenity, Joviality, Attentiveness, and Self-Assurance. Greater daily levels of overall positive affect, as well as the lower order facets of Joviality, Self-Assurance, and Attentiveness, were predicted by heightened BAS sensitivity. In contrast, the facet of Serenity demonstrated minimal associations with BAS sensitivity. The study findings support a multi-faceted structure of positive affect and suggest that certain facets may be more closely related to risk for bipolar disorder. Specifically, Joviality and Self-Assurance may represent maladaptive forms of positive affect, whereas Serenity may function as a protective element against bipolar disorder.

The present study investigates the language phenomenon of stimulus equivalence in children with Autism Spectrum Disorder. Stimulus equivalence is comprised of 3 main concepts: reflexivity, symmetry, and transitivity. Specifically, the researcher evaluated the ability to teach, test, and transfer sequential reflexivity across two participants. Two 4-year-old children diagnosed with Autism Spectrum Disorder participated in the study. Methods were derived from the program: Reflexivity: Pictures – 2A, along with a yes/no response modification to suite both of the participant’s current level of developmental skills. The results suggest that the PEAK-E curriculum was effective in training and testing both children to establish reflexivity across stimulus set one. In addition, both participants demonstrated a transfer of stimulus function to an untrained stimulus set two once the trained stimulus set one was mastered.

Autism spectrum disorder (ASD) is a long-standing mental condition characterized by hindered mental growth and development. In 2018, 168 out of 10,000 children are said to be affected with Autism in the USA. As these children move to adulthood, they have difficulty in communicating with others, expressing themselves, maintaining eye contact, developing a well-functioning motor skill or sensory sensitivity, and paying attention for longer period. Some of these abnormalities, however, can be gradually improved if they are treated appropriately during their adulthood. Studies have shown that people with ASD can enhance their social-interactive skills by playing video games. During the past decades, however, educational games have been primarily developed for autistic children, but not for autistic adults. We have developed a gaming and recommendation system that suggests therapeutic games to autistic adults which can improve their social-interactive skills. The gaming system maintains the entertainment value of the games, to make sure people are interested in playing them, whereas the recommendation system suggests appropriate games for autistic adults to play. Customizable games are designed and implemented in Minecraft such that each game focuses on enhancing different weakness areas in autistic adults based on games that the users have not explored in the past. The effectiveness of the gaming and recommendation system is backed up by an empirical study which shows that recommending therapeutic games can aid in the improvement of social-interactive skills of adults with ASD so that they can live a better life in the years to come.

Psychology
Ph.D.
In this study, I tested predictions of the Behavioral Approach System (BAS) model as applied to the course of bipolar spectrum disorders. In this model, when a vulnerable individual experiences a BAS activation-relevant event, the weak regulatory strength of the BAS interacts with pre-event BAS state and is likely to lead to hypomania/mania. In contrast, when a vulnerable individual experiences a BAS deactivation-relevant event, the weak regulatory strength of the BAS interacts with pre- event BAS state and is likely to lead to depression. A secondary goal of this study involved comparing the BAS model to the cognitive-vulnerability stress model of bipolar disorder. Toward this end, data from a sample of 217 individuals (112 individuals with a diagnosis in the bipolar spectrum and 105 demographically similar, normal controls) participating in the Longitudinal Investigation of Bipolar Spectrum Disorders (LIBS) Project, a two-site prospective examination of the role of BAS, cognitive styles, and life events in the course of bipolar disorders among college students, were analyzed. The results of this study suggest that there is some support for both the BAS model and the cognitive-vulnerability stress model. Specifically, BAS-relevant cognitive styles, in interaction with congruent positive life events, predicted hypomanic episodes. There was less support for either model in the prediction of depression. There was some support for BAS sensitivity and BAS-relevant events each predicting the course of bipolar disorder. However, there was no support for the interaction of BAS sensitivity and BAS-relevant events predicting the type and number of mood episodes. As such, this study found more support for a BAS-related cognitive vulnerability-stress model, as compared to the "pure" BAS model, as applied to bipolar spectrum disorders. Following a review of the results, strengths and limitations, as well as clinical implications and potential future research directions are discussed.
Temple University--Theses

Autism spectrum disorder (ASD) is a group of developmental disabilities characterized by impairments in social interaction and communication and by difficulties in emotion recognition and regulation. There is currently no cure for autism but psychosocial interventions and medical treatments exist. However, very few of them have been trialed on young children and others pose limitations. Strengthening young children's capacity to manage their emotions is important for academic success. Thus it becomes important to design and test the feasibility of an appropriate methodology that can teach emotion regulation to young children (age 3-6 years) with ASD. This thesis addresses the problem by proposing a novel framework that integrates physiology with Cognitive Behavior Theory to enable emotion regulation in the target population by exposing them to real-time stressful situations. The framework uses a feedback loop that measures the participant's physiology, estimates the level of stress being experienced and provides an audio feedback. The feasibility of the individual building blocks of the framework was tested by conducting pilot studies on nine typically developing children (age 3-6 years). The attention capturing capacity of different audio representations was tested, and a stress profile generating system was designed and developed to map the measured physiology of the participant on to a relative stress level. 33 out of 43 instances of audio representations proved to be successful in capturing the participants' attention and the stress profiles were found to be capable of distinguishing between stressed and relaxed state of the participants with an average accuracy of 83%.
Master of Science

"The present studies investigated the issue of potential explanatory mechanisms for the observed association between panic disorder (PD) and the development of cardiovascular disease (CVD). Specifically, this research aimed to elucidate more clearly the contribution of psychological variables. physical processes and social relations to the onset of cardiopathology."
Doctor of Clinical Psychology

This thesis presents a series of studies that explore the creation of an autism friendly environment within the Criminal Justice System. The first study explored the perception and understanding of police officers regarding autism. It was found that although police officers have some knowledge of the traits of Autism Spectrum Disorder, they fail to accommodate for these when planning a witness or a suspect interview. Appropriate Adults support vulnerable suspects in custody and the second study found that Appropriate Adults also failed to apply what they know about autism to their work. However, the study revealed instances where the characteristics of autism can damage the progress of an interview. Hence, the study concluded that to be effective, Appropriate Adults must monitor behaviours which may arise as a result of internal characteristics. Study 3 examined how people from the higher end of the autism spectrum understand the current caution. It was found that people with autism performed comparably to those from the general population. Overall both populations where not very good at explaining the caution in full, and performed poorly when explaining its function. An alternative version of the caution was devised for study 4, however this had mixed results. It was useful to participants when they explained the caution one sentence at a time, and helped in the understanding of its function. However, there were damaging effects. People with autism performed poorly when explaining the sentence which informs that what is said can used as evidence. Study 5 attended to people from the higher end of the autism spectrum as witnesses. Results showed that the Mental Reinstatement of Context and Sketch plan Mental Reinstatement of Context both had a positive impact on the recall of information. Additionally the use of memory jogs, a colour search and an alphabet search helped people with autism to provide additional pieces of information, particularly relating to person descriptors.

Psychosocial support from family is important in outpatient treatment programs for individuals with depressive disorder. The purpose of this phenomenological study was to explore the lived experiences and perceptions of parents of patients with depressive disorder regarding intensive outpatient treatment. The research question was what are the experiences and perceptions of parents of patients with depression regarding their role as caretakers in intensive outpatient treatment? The conceptual framework was a biopsychosocial framework and family systems theory. Content analysis was used to analyze data provided from interviews with parent participants (n = 8). Many participants reported high levels of involvement with various forms of support. They maintained positive relations with professionals, were involved in patient socialization, and facilitated adherence to patients' treatment plans. The results of this study indicated that family caregivers experienced ambivalent emotions toward their roles and patients. Findings also indicated experiences of exhaustion, strong emotions about the burden of having to support the patient, and concern for their own and the rest of the family's well-being. Future researchers should study these aspects further. Researchers, clinical practitioners, and policy makers must increase efforts to support those who help family members suffering from depression to intensify the search for effective ways to reduce the toll on those caregivers. Because of these findings, researchers could expand literature to illuminate the decisions and practices of psychotherapists, leading to improvements in intensive treatment programs for both patients and their caretakers. This study impacts social change by providing insights to aid policy makers in ensuring that outpatients receive the best treatment program available and that their primary caretakers are psychologically prepared and healthy.

Background: Research into the benefits of exercise for individuals with Bipolar Disorder (BD) is limited and no current guidelines exist around recommending exercise during a hypomanic/manic state. The Behavioural Activation System (BAS) dysregulation theory is a popular model that attempts to explain the link between approach motivation (AM) and the difficulties that individuals with BD experience. It may offer an explanation for the ‘upward spiral’ reported by individuals with a diagnosis of BD in response to certain types and intensities of exercise. This study looked to investigate the impact of different intensities of exercise on the maintenance of AM levels. The presence of hypomanic traits and how these interacted between AM and exercise was also of interest. Method: Participants filled out an online pre-screening questionnaire identifying hypomanic traits. 61 then completed a computer task designed to induce higher levels of AM before taking part in one of three 15 minute activities (sedentary, moderate exercise or vigorous exercise). Various measures linked to hypomanic symptoms were taken during testing. Results The main findings indicated that vigorous exercise significantly increased individuals AM levels in comparison to moderate or no exercise. This relationship was not however found to be moderated by the presence of hypomanic traits. Conclusions: Vigorous exercise seems to have a greater impact on AM levels regardless of an individual’s levels of hypomanic traits. This has implications in terms of the type of exercise should engage in when experiencing hypomania. Any recommendations however within this study should be taken in light of the limitations identified. Further research replicating these results with a larger sample or using a BD population are recommended.

Affecting 1 in 68 children, Autism Spectrum Disorder (ASD) is one of the most prevalent cognitive disorders in the global population. Symptoms of ASD, although typically not life-threatening, have a large impact on the social wellbeing of diagnosed individuals. Inflammation in the brain, or neuroinflammation, has previously been shown to increase the severity of the behavioral deficits associated with ASD. The exact etiology of the neuroinflammation observed in ASD remains unclear, especially in regards to protein expression that initiates the inflammatory pathway. This experiment examines two specific markers of neuroinflammation, glial fibrillary acidic protein (GFAP) and myelin-associated glycoprotein (MAG) in a previously characterized mouse model of ASD. GFAP is astrocyte-specific, cytoplasmic, and has been shown to be upregulated in trauma or disease pathologies in the brain. MAG is found in the membrane of oligodendrocytes and is a major regulator of development and regeneration of nervous tissue. Control C57bl/6j mice and ASD-representative BTBR T+tf/J (BTBR) mice were sacrificed twenty-one days after birth. Immunoblotting was performed on cingulate cortical tissue using anti-GFAP and anti-MAG primary antibodies to quantify levels of GFAP and MAG protein expression between the control and ASD models. These findings provide further evidence that changes in GFAP and MAG expression may alter the neuroinflammatory pathways observed in ASD-representative mice.

According to the regulations contained in the Social Services Act (SFS 2001:453), Swedish social services have a legal responsibility to provide support, care, and treatment for individuals with substance use problems.  This law mandate those who are responsible to provide treatment to motivate drug users to actively seek treatment on a voluntary basis, ensuring an end to their dependence on drugs. Studies have shown that although the treatment system largely focuses on promoting abstinence, about two-thirds of client’s relapse into substance use within one year after completing treatment. This dissertation focuses broadly on clients who repeatedly enter and use treatment for substance use disorders in the Swedish addiction treatment system. The aim of this thesis is to examine and identify the population groups who are repeated treatment users of the Swedish treatment system for substance use disorder, including both the voluntary treatment and compulsory care. This thesis was based on three national level databases. The results showed that clients with a higher degree of problems and problems in different areas of life also had an increased risk of having treatment for substance use disorder repeatedly. Clients who were older, men, reported more years of polydrug and alcohol use to intoxication, reported more compulsory care episodes for substance use, had ever been charged with crime, had ever been in inpatient mental health treatment, and had a higher ASI mental health symptom composite score, were significantly more likely to report more voluntary addiction treatment episodes. The strongest significant association with the number of treatment episodes was the number of compulsory treatment episodes for alcohol and drugs. Individuals who experienced prior compulsory care including mandatory treatment through LVU (law (1990:52)), been in prison, and had children mandated to out-of-home care, were more likely to have two or more entries in the compulsory care system for substance use disorder. In addition, this analysis showed that 59% of clients mandated to compulsory care dropped-out during their compulsory care episode, and that younger clients were significantly more likely to drop-out. Those who drop-out were significantly more likely to experience negative outcomes, i.e. additional sentence to compulsory care and higher risk of mortality.  A hierarchal logistic regression model also identified that individuals with riskier childhood conditions were more likely to have had repeated entries to compulsory care for substance use disorder. The indirect effects showed that a family history of substance use disorder and psychiatric problems are both associated with higher probability of institutional care as a child i.e. LVU, and that in turn, mandated childhood institutional care is related to repeated compulsory care intakes as an adult. Individuals who use treatment for substance use disorder repeatedly have a higher degree of problems i.e. an exposed and problematic group of individuals characterized by problem in several different areas of life. Growing up in a home environment with unfavorable conditions, mandated care before the age of 18 (LVU), compulsory care for substance use disorder as an adult, children taken into out-of-home care, and crime are the factors that are primarily associated with repeated treatment for substance use. A change in the view of treatment for clients in need of repeated use of treatment seems important, and access to adapted continuous care efforts are crucial to counteract the risk of relapse after a treatment episode of voluntary or compulsory care. Further, it seems important to motivate the client to complete the compulsory care without any deviation, since this seems to have positive effects on their substance use disorder.

Many psychological problems in adulthood have their roots in childhood and adolescence. This is particularly true for personality disorders (PDs). In order to identify young people with PD traits before their problems become pervasive, we need reliable and valid assessment tools. This volume includes three papers seeking to examine the usefulness of the Achenbach System of Empirically Based Assessment (ASEBA) for measuring PD traits in young people. Part 1 is a systematic review of cross-sectional and longitudinal studies that used the ASEBA to investigate the internalising and externalising problems of young people presenting with (or who later developed) personality difficulties. The majority of the studies examined antisocial and borderline PD. The review concluded that there was consistent evidence of criterion validity for a few ASEBA scales but the ASEBA did not have adequate psychometric properties for accurately identifying young people with PD. Part 2 is an empirical paper that used a large database created for audit purposes in a community-based psychotherapy and counselling service for young people. The ASEBA profiles of young people with PD traits and PD-related presenting problems were examined. This paper also describes the development and psychometric evaluation of two new, PD-related ASEBA scales. Finally, Part 3 is a critical appraisal of the research undertaken. It discusses epistemological and methodological aspects of the work and reflects upon the proposed changes in the conceptualisation of PD in the updated diagnostic system. This paper also highlights the clinical dilemmas related to diagnosing PD before adulthood.

Attention-deficit/hyperactivity disorder (ADHD) likely involves fundamental alterations in self-regulation. These problems typically have been viewed as involving disruptions in the regulation of cognition and behavior. However, they also have been hypothesized to involve disruptions in emotion regulation. If so, parenting behaviors may take on renewed importance in ADHD, because parents play an essential role in children developing the ability to regulate their emotions independently. Three studies examined the association between emotion regulation and ADHD. Study 1 examined autonomic nervous system functioning during the experience and regulation of both positive and negative emotions. Study 2 examined coherence among autonomic and behavioral emotional systems. Finally, Study 3 examined the roles of parenting behavior, parental expressed emotion, and child autonomic nervous system functioning. In Studies 1 and 2, participants with ADHD and typically developing youth aged 7 to 11 years old completed an emotion induction and suppression procedure. For Study 3, participants completed a parent-child interaction task coded for parental behavior, and parents completed a five-minute speech sample coded for expressed emotion. Electrocardiogram and impedance cardiography were monitored for children across all three studies. The following results were notable. In Study 1, children with ADHD showed atypical autonomic inflexibility (i.e., elevated parasympathetic and sympathetic responding across task conditions). Additionally, children with ADHD were divided according to levels of prosocial behavior. Unlike other children with ADHD, children with very low levels of prosocial behavior displayed blunted autonomic activity across task conditions. In Study 2, specific patterns of reduced coherence among emotion regulatory systems (i.e., facial affective behavior and autonomic nervous system reactivity) were observed among children with ADHD. Finally, in Study 3, high levels of parental expressed emotion were associated uniquely with ADHD, even after controlling for comorbid symptoms. In contrast, parental intrusiveness was associated uniquely with child oppositional defiant and low prosocial behavior, even after controlling for ADHD symptoms. Furthermore, specific, different patterns of autonomic reactivity during the parent-child interaction were associated with ADHD and oppositional defiant behaviors. Across these studies, it is concluded that intrinsic and extrinsic emotion and emotion regulatory systems are disrupted among children with ADHD.

Persons suffering from Attention deficit/hyperactivity disorder (ADHD) struggle with complications within the functions that regulate and control the brain activities, due to deficiencies in these functions within the affected nerve-paths. ADHD is a cognitive function impairment characterised by inattention, impulsiveness and over activity. According to Diagnostic and Statistic Manual of Mental Disorders, American Psychiatric Association (DSM-IV), certain diagnostic criteria of ADHD must be fulfilled in order for a person to be diagnosed with ADHD. The everyday problems caused by ADHD are individual and medication can have positive effects relieving the person’s impairing behaviour. The study is based on scientific literature, three quantitative scientific articles and preview material from the last study by Johnson, Fransson, Kadesjö & Gillberg, presently being scrutinised. Swedish as well as English literature has been used. The purpose of this study is to shed some light upon whether medication facilitates the child’s school situation. The result deals with the ADHD diagnosis and pharmacological therapy involving drugs that stimulate the central nervous system, as well as naturopathic medicine like Omega-3/6. The pedagogical aspect for children with ADHD in school has been observed and evaluated. In this matter it is important for the pedagogue to encourage the child by letting it find out that it can manage more than it thinks.

AMPA receptors play a key role in synaptic glutamatergic transmission in both physiological and pathological conditions of the central nervous system. Particularly, I have tried to analyze and to give some answers on aspects that are still unexplored or controversial using synaptosomes (pinched off nerve terminals) as experimental model. As a first approach I focused on the composition of the GluA subunits, which is a requisite to encompass the role of AMPA receptors in the physiological conditions but also in neurological disorders. By using the “immuno- pharmacological approach”, which consists in using antibodies recognizing the outer sequences of the target protein as a pharmacological tool, I propose that cortical AMPA autoreceptors consist of GluA2-GluA3 subunits assembly, which move in-out synaptosomal plasma membranes in a constitutive manner. The commercially available anti-GluA2 and anti-GluA3 antibodies hugely facilitated the releasing activity of the AMPA autoreceptors by stabilizing them in plasma membranes. Interestingly, the consequent presence of the antigen-antibody complex in synaptosomal plasma membranes caused the activation of complement through the classic pathway, then reinforcing the complement-induced evoked releasing activity of the immune complex in these terminals. The results unveiled therefore a complement-dependent and a complement-independent pathway that could account for central derangements and excitotoxic events occurring during central autoimmune diseases typified by anti-GluA autoantibodies overproduction. It is the case of patients suffering from the frontotemporal dementia (FTD) that have elevated levels of circulating anti-GluA3 autoantibodies. Contrary to expectation, however, the incubation of mice cortical synaptosomes with FTD patients’ CSF (cerebrospinal fluid) positive for anti-GluA3 autoantibodies causes the reduction of the glutamate release evoked by the agonist AMPA, instead of the predicted amplification. Further studies are required to address the point. AMPA receptors are also potential targets of detrimental events in stress-related diseases, which are recapitulated by several animal models, including the perinatal restrain stress (PRS) rat model. By using this model, I investigated the long-term programming effects of PRS on the glutamatergic synapse in males and females. I demonstrated that male PRS rats displayed a reduced expression of GluA2 and GluA3 subunits in the dorsal hippocampus and prefrontal cortex in old age rats (20-22 months), in line with their impaired performance in the behavioral test. These results confirmed that the impaired glutamatergic transmission lie at the core of the pathological phenotype induced by PRS. Remarkably, the long-term programming effects triggered by PRS are strictly sex-dependent. Particularly, PRS mainly affects males whereas females seem to be protected against the detrimental effects triggered by early life stress. Taken together these results strengthened the importance of understanding more about the role of AMPA receptors subunits in the brain functions.

碩士
國立臺北大學
法律學系一般生組
105
In order to solve the criminal problems of mental disorders, we should value the treatment system of mental disorder criminals. As a result, in this thesis, I intend to review and analyze the treatment system of mental disorder criminals in Taiwan. I hope that the research result can be beneficial to the development of the treatment system of mental disorder criminals. The methodologies adopted in this thesis are literature review, case study and comparative research method. The Chapter 1, Introduction. It describes the research motivation, the methods, and the scope of the study. The Chapter 2, Commitment. It describes the legislative purpose of the commitment, the elements the commitment, and how to enforce the commitment. In my opinion, there are some problems of commitment. In Chapter 3, it discusses that is there any possible way to help mental disorder criminals receive treatment. In our country, deferred prosecution, probation, compulsory hospitalization and compulsory community treatment may the way to help mental disorder criminals receive treatment. In Chapter 4, how to help mental disorder criminals receive treatment after commitment will be discussed. I suggest that conditions of supervision in Germany is worth our reference. The Chapter 5, Collaborative treatment system. It describes that the importance of the collaboration between criminal system and mental health system in treatment enforcement. In our country, the enforcement of deferred prosecution with psychiatric treatment, probation with psychiatric treatment , after care service shown the collaboration between criminal system and mental health system. Furthermore, in my point of view, to plan the treatment system of mental disorder criminals which the collaboration between criminal system and mental health system be valued, the Sequential Intercept Model can be used.The Chapter 6, Conclusion.

碩士
國立臺灣科技大學
高分子系
97
The purpose of this study was to develop an intelligent recognition system for vocal cord disorders. The image processing technology and neural networks were applied to identify different disease conditions of vocal cords, including the presence of paralysis, tumor, malignant cancer, or no diseases. We first changed three random sets of original obtained images into a grayscale format, followed by applying histogram equalization to obtain a good contrast. We then used statistical threshold to segment the processed images. The binary images were lastly computed by labeling, dilation and erosion to obtain the position of the glottis. The features of the three sets of images would be the input of the neural network. After testing 95 samples, the experimental results reveal that the third set had the best recognition rate reaching 93.6%. The results of this experiment support that the intelligent recognition system has the ability to identify vocal cord disorder. Thereby the problems obtained from misdiagnosis and subjective knowledge in the medical field could be reduced effectively.

The functional compartmentalization underlying neuronal polarity makes tightly regulated intracellular transport between the cell body, axons, and dendrites essential for proper development and homeostatic maintenance. Disruptions to neuronal trafficking are a major cause of neurodegenerative disease. Pathogenic variants in the microtubule motor protein KIF1A cause KIF1A Associated Neurological Disorder (KAND), a spectrum of rare neurodegenerative conditions. KAND is clinically and genetically heterogeneous, with a broad phenotypic spectrum and over a hundred pathogenic variants identified. KAND is poorly understood at both the clinical and molecular level, and there is currently no treatment. This work characterizes the natural history of KAND and describes a novel heuristic severity score. This severity score is then used to show how the location of pathogenic missense variants within the KIF1A motor domain correlates with disease severity, providing evidence the clinical phenotypic heterogeneity in KAND reflects and parallels the molecular phenotypes. Insights from the neuropathology of deceased KAND patients is used to focus a histopathologic assessment of the C3-Kif1aLgdg mouse model. C3-Kif1aLgdg/Lgdg mice have a cerebellar axonal torpedo phenotype, paralleling some of the pathological changes seen in the patients. Phenotypically, the C3-Kif1aLgdg mice were found to recapitulate some of the symptoms seen in patients including progressive spasticity and gait abnormalities associated with hind limb paralysis. To model the disease at a cellular level, iPSCs were derived from affected individuals and successfully used to generate neural stem cells and neurons. These patient-derived neurons were found to have increased markers of protein aggregates, a cellular phenotype that can be used to test potential treatments. Taken together, these studies provide foundational knowledge for future therapeutic development.