Schizophrenia is among the most debilitating mental disorders, yet the pathophysiology remains unclear. The basal ganglia, a region of the brain involved in motor, cognitive, and sensory processes, may be involved in the pathophysiology of schizophrenia. Some, but not all, neuroimaging studies suggest abnormalities of the basal ganglia in schizophrenia. However, previous studies have examined whole basal ganglia nuclei as opposed to using a unified basal ganglia complex that incorporates anterior-posterior divisions, dorsal-ventral divisions, and gray-white matter segmentation. The hypothesis for the present study was that basal ganglia sub-regions forming functionally relevant subdivisions might be different in schizophrenia. Magnetic resonance imaging scans were acquired from 25 first-episode schizophrenia subjects and 24 healthy subjects. Using manual and automated neuroimaging techniques, total and segmented (gray-white matter) volumes were obtained for the caudate, putamen, and globus pallidus. For the striatum (caudate and putamen), total and segmented volumes were obtained for their respective sub-regions. These sub-regions were restructured into associative, limbic, and sensorimotor subdivisions. Schizophrenia subjects had 6% smaller gray matter volumes for the caudate and 8% smaller gray matter volumes for the associative striatum relative to healthy subjects. Basal ganglia function was studied by examining performance on a neuropsychological test that assesses frontostriatal functioning. For male subjects there was a significant negative correlation between volume of the associative striatum and performance on the neuropsychological test (r=-0.57, p=0.03). Smaller volumes of the associative striatum were associated with more errors on the neuropsychological test. This test was specific to the associative striatum, as another neuropsychological test did not reveal any correlation. In schizophrenia subjects, the relationship between basal ganglia volumes and motor symptoms severity was examined. For antipsychotic-naive subjects there was a significant negative correlation between volume of the motor striatum and severity of Parkinsonism (r=-0.65, p=0.03). The present study suggests that total basal ganglia nuclei volumes are not different in schizophrenia, but gray matter volumes of total basal ganglia nuclei and subdivisions forming functional units may be different in schizophrenia. Structural abnormalities involving the basal ganglia may lead to disrupted functional circuits in schizophrenia.

Schizophrenia is among the most debilitating mental disorders, yet the pathophysiology remains unclear. The basal ganglia, a region of the brain involved in motor, cognitive, and sensory processes, may be involved in the pathophysiology of schizophrenia. Some, but not all, neuroimaging studies suggest abnormalities of the basal ganglia in schizophrenia. However, previous studies have examined whole basal ganglia nuclei as opposed to using a unified basal ganglia complex that incorporates anterior-posterior divisions, dorsal-ventral divisions, and gray-white matter segmentation. The hypothesis for the present study was that basal ganglia sub-regions forming functionally relevant subdivisions might be different in schizophrenia. Magnetic resonance imaging scans were acquired from 25 first-episode schizophrenia subjects and 24 healthy subjects. Using manual and automated neuroimaging techniques, total and segmented (gray-white matter) volumes were obtained for the caudate, putamen, and globus pallidus. For the striatum (caudate and putamen), total and segmented volumes were obtained for their respective sub-regions. These sub-regions were restructured into associative, limbic, and sensorimotor subdivisions. Schizophrenia subjects had 6% smaller gray matter volumes for the caudate and 8% smaller gray matter volumes for the associative striatum relative to healthy subjects. Basal ganglia function was studied by examining performance on a neuropsychological test that assesses frontostriatal functioning. For male subjects there was a significant negative correlation between volume of the associative striatum and performance on the neuropsychological test (r=-0.57, p=0.03). Smaller volumes of the associative striatum were associated with more errors on the neuropsychological test. This test was specific to the associative striatum, as another neuropsychological test did not reveal any correlation. In schizophrenia subjects, the relationship between basal ganglia volumes and motor symptoms severity was examined. For antipsychotic-naive subjects there was a significant negative correlation between volume of the motor striatum and severity of Parkinsonism (r=-0.65, p=0.03). The present study suggests that total basal ganglia nuclei volumes are not different in schizophrenia, but gray matter volumes of total basal ganglia nuclei and subdivisions forming functional units may be different in schizophrenia. Structural abnormalities involving the basal ganglia may lead to disrupted functional circuits in schizophrenia.

Schizophrenia is among the most debilitating mental disorders, yet the pathophysiology remains unclear. The basal ganglia, a region of the brain involved in motor, cognitive, and sensory processes, may be involved in the pathophysiology of schizophrenia. Some, but not all, neuroimaging studies suggest abnormalities of the basal ganglia in schizophrenia. However, previous studies have examined whole basal ganglia nuclei as opposed to using a unified basal ganglia complex that incorporates anterior-posterior divisions, dorsal-ventral divisions, and gray-white matter segmentation. The hypothesis for the present study was that basal ganglia sub-regions forming functionally relevant subdivisions might be different in schizophrenia. Magnetic resonance imaging scans were acquired from 25 first-episode schizophrenia subjects and 24 healthy subjects. Using manual and automated neuroimaging techniques, total and segmented (gray-white matter) volumes were obtained for the caudate, putamen, and globus pallidus. For the striatum (caudate and putamen), total and segmented volumes were obtained for their respective sub-regions. These sub-regions were restructured into associative, limbic, and sensorimotor subdivisions. Schizophrenia subjects had 6% smaller gray matter volumes for the caudate and 8% smaller gray matter volumes for the associative striatum relative to healthy subjects. Basal ganglia function was studied by examining performance on a neuropsychological test that assesses frontostriatal functioning. For male subjects there was a significant negative correlation between volume of the associative striatum and performance on the neuropsychological test (r=-0.57, p=0.03). Smaller volumes of the associative striatum were associated with more errors on the neuropsychological test. This test was specific to the associative striatum, as another neuropsychological test did not reveal any correlation. In schizophrenia subjects, the relationship between basal ganglia volumes and motor symptoms severity was examined. For antipsychotic-naive subjects there was a significant negative correlation between volume of the motor striatum and severity of Parkinsonism (r=-0.65, p=0.03). The present study suggests that total basal ganglia nuclei volumes are not different in schizophrenia, but gray matter volumes of total basal ganglia nuclei and subdivisions forming functional units may be different in schizophrenia. Structural abnormalities involving the basal ganglia may lead to disrupted functional circuits in schizophrenia. / Medicine, Faculty of / Graduate

Thesis advisor: Judith Shindul-Rothschild / Clinical Characteristics Of People In Randomized Clinical Trials Of First Episode Schizophrenia Spectrum Disorders: Attrition Versus Non-Attrition Groups Submitted by Joanne D. Wojcik PhD, RN Dissertation Advisor Judith Shindul-Rothschild, PhD, RN Abstract Background: Early identification of psychosis and intensive treatment has been the focus of the treatment of people with a first episode (FE) schizophrenia spectrum disorder (SSD). Attrition rates in studies of people in the first episode are high, which makes it difficult to understand the meaning of the study outcomes. High attrition rates affect the validity of a study by decreasing its power and the study's ability to detect differences between treatment groups. Additionally, the people who leave a study may be different from those who stay in demographic, illness and treatment characteristics. Method: This study is a secondary analysis of a group of FE SSD participants enrolled in one of three separate double-blind, randomized, drug trials. The variables were first analyzed across the three drug study data sets to determine if the patient populations are comparable across the three studies to allow for the merging of the data. Exploratory and descriptive statistics of study participants were conducted in a comparison of the three studies, for the merged group, and for the attrition and non-attrition groups. Effect sizes (Cohen's d) were calculated for each variable in the individual studies and in the merged dataset for the magnitude of difference between the attrition and non-attrition groups. Results: The three studies were merged after analysis found no consistent difference in demographic and illness characteristics between the three studies. There was no significant difference between the attrition and non-attrition groups in the merged data in demographic and illness characteristics. Treatment characteristics consistently found lack of efficacy and patient withdrawal of consent to be the two most frequent reasons for attrition from the studies. In addition, participants receiving a typical agent were less likely to complete the study. Effect size calculations found attrition group to more likely be Caucasian, with a lower median income. The attrition group had more years of education, but was not in school in the year previous to hospitalization. Conclusion: Historically, attrition is a major problem in clinical trials of people in a first episode of schizophrenia spectrum disorders. People receiving typical antipsychotic medication are more likely to leave a study. Most common reasons for attrition include lack of efficacy and withdrawal of consent / Thesis (PhD) — Boston College, 2009. / Submitted to: Boston College. Connell School of Nursing. / Discipline: Nursing.

Thesis (PhD)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Prospective, longitudinal clinical studies in first-episode schizophrenia have become relatively commonplace over the past two decades or more and have provided a wealth of useful information regarding the clinical presentation, treatment, course and outcome of the illness. However, there remain several unanswered questions. The majority of the studies have been conducted in upper income countries using often costly medication with heterogeneous samples. While the overall outcome of patients showed some progress, there is room for improvement yet. The overall aim of the dissertation was to study the clinical, biological and functional aspects of outcome in first episode schizophrenia in a resource constrained setting. We conducted a prospective, non-comparative, longitudinal study over 12 months assessing the efficacy and tolerability of a cost effective, long-acting injectable antipsychotic (LAI; flupenthixol decanoate) combined with an assertive monitoring program (AMP) among first-episode schizophrenia patients. Efficacy was measured by examining rates of response, remission and relapse, as well as quality of life and social and occupational functioning. Tolerability of our intervention was assessed by measuring extrapyramidal symptoms, and weight and metabolic changes. We also examined the evolution of treatment refractoriness by studying the rates of non-response, and other associated predictor and outcome features. We found high rates of acceptance and adherence to the LAI and AMP. Seventy percent of our patients completed the 12 months of treatment. Treatment response was achieved by 82% of the participants and 60% achieved remission. Although 19% of our patients relapsed, the majority of the relapses were mild and did not require hospitalisation. Patients experienced significant quality of life and social and occupational functioning improvements. We found mild rates of extrapyramidal effects, present in only a third of our cohort. The majority of the extrapyramidal effects were treated with anticholinergics or propranolol. Only 3% of our patients developed transient dyskinesia over the duration of the study. However, our cohort gained considerable weight, with statistically significant increases in BMI (p< .0001) and waist circumference (p=0.0006). Our cohort also experienced significant deleterious changes to their lipid profiles. Of particular concern was the increase in triglycerides (p=0.03) and a significant decrease in high density lipoprotein (p=0.005) leading to a 91% increase in the triglyceride/high density lipoprotein ratio. With regards to emerging treatment refractoriness, 12% of our patients met our pre-defined criteria for non-response. Non-responders were younger and at baseline showed more prominent disorganised symptoms, poorer social and occupational functioning, poorer quality of life for psychological, social and environmental domains, more prominent neurological soft signs (NSS), and lower BMI. At endpoint the non-responders were characterised by higher levels of symptomatology in all domains; poorer functional outcome, poorer quality of life and greater cognitive impairments. They also had more prominent NSS and a lower BMI. The strongest predictors of non-response were prominent baseline NSS and poor early (7 weeks) treatment response. In conclusion, the combination of an LAI with an AMP may be an effective and safe intervention in firstepisode schizophrenia, and may be particularly suitable for resource-constrained settings. The risk of weight gain and metabolic syndrome associated with antipsychotic treatment in first-episode schizophrenia are not restricted to second generation antipsychotics and low-potency first-generation antipsychotics. Ensuring effective treatment for first episode schizophrenia patients is a global problem, and likely to be under-recognised in LMICs. / AFRIKAANSE OPSOMMING: Oor die afgelope twee dekades het toenemend meer longitudinale kliniese studies, wat eerste episode skisofrenie bestudeer, die lig gesien. Die studies het ‘n magdom van waardevolle inligtng oor die kliniese voorkoms, behandeling, verloop en uitkomste van die siekte opgelewer. Die meerderheid van die studies is egter in hoë inkomste ontwikkelde lande gedoen met pasiënte wat duur medikasie gebruik en hoofsaaklik in heterogene steekproewe. Alhoewel dit blyk uit hierdie studies dat daar oor die algemeen vordering gemaak word ten opsigte van die behandeling van pasiënte is daar steeds ‘n gebrek aan voldoende inligting oor die onderwerp veral in minder gegoede, ontwikkelende lande. Die oorhoofse doel van hierdie proefskrif is om binne ‘n hulpbron beperkte konteks die kliniese, biologiese en funksionele aspekte van pasiënt -uitkomste in eerste episode skisofrenie te ondersoek. Ons het ‘n longitudinale studie gedoen waarin ons die effektiwiteit en toleransie van ‘n enkele antipsigotiese medikasie vir 12 maande nagevors het. Die medikasie wat ons ondersoek het, is flupenthixol decanoate en word deur ‘n inspuiting gegee en die medikasie word dan geleidelik deur die liggaam geabsorbeer. As deel van die behandeling het ons pasiënte ook streng gemonitor. Ons het die effektiwiteit van die behandeling gemeet nagelang van hoe pasiënte reageer op die behandeling, hoeveel pasiënte in remissie gaan en terugval, en ook pasiënte se kwaliteit van lewe en hulle sosiale en beroepsfunksionering. Ons het toleransie gemeet nagelang van pasiënte se gewig en metaboliese verandering sowel as die voorkoms van medikasie geïnduseerde newe-effekte. Verder het ons pasiënte wat nie op medikasie gereageer het nie ondersoek sowel as die aspekte wat moontlik hiernee verband hou. Ons het bevind dat die meerderheid van pasiënte hulle medikasie getrou geneem het en ook die streng monitering aanvaar het. Sewentig persent van die pasiënte het hulle 12 maande behandeling voltooi, 82% het op die medikasie gereageer en 60% het in remissie ingegaan. Alhoewel 19% van die pasiënte teruggeval het, was dit nie so ernstig dat ons hulle moes hospitaliseer nie. Pasiënte het beduidende verbetering ten opsigte van hulle kwaliteit van lewe en sosiale en beroepsfunksionering getoon. Ons het slegs ‘n gematigde mate van medikasie geïnduseerde newe-effekte opgemerk en alleenlik by ‘n derde van die kohort. In die meerderheid van gevalle het ons die newe-effekte met anticholinergics of propranolol behandel. Slegs 3% van die pasiënte het gedurende die verloop van 12 maande die kondisie transient dyskinesia ontwikkel. Ongelukkig het ons kohort geweldig baie gewig opgetel en die toename in pasiënte se BMI (p< .0001) en middellyf omtrek (p=0.0006) was statisties beduidend. Ons het ook bevind dat veranderinge in ons kohort se lipied profiele kommerwekkend is veral as in ag geneem word dat die toename in trigliseriede (p = 0,03) en die beduidende afname in die hoë digtheid lipoproteïen (p = 0,005) gelei het tot ‘n 91% verhoging in trigliseriede: hoë digtheid lipoproteïen verhouding.

Cognitive deficit is now considered to be a core feature of schizophrenia, which significantly influences psychosocial functioning in individuals with this illness. The aim of this study is to analyze the cognitive performance during the first year after the first episode of the illness and cognition related to psychosocial functioning. A total of 28 people hospitalized after the first psychotic episode of schizophrenia F20 according to ICD-10 participated in our study and underwent measurements of cognitive functions by the international MCCB battery. They were also evaluated by the PANSS (Scale of positive and negative symptoms) and PSP (range of personal and social performance). After one year from the first measurement for re-examination, 20 patients made an appearance. In 75% of the sample (n = 28), a cognitive deficit below 1.5 standard deviations below the normative average, i.e. below 35 T-score, was detected, at least in one of the measured domains. Speed of processing was the most impaired domain (T < 35), Reasoning and problem solving was the least attenuated domain (T > 40). The resulting analysis (paired t-test) showed a significant improvement one year after first-episode schizophrenia in domains Speed of processing (p = 0,018) and Reasoning and problem solving (p = 0,023). The...

No description available.

No description available.

No description available.