Dissertation (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2006. / Vita. Bibliography: p. 125-165.

INTRODUCTION: Major depressive disorder (MDD) is characterized by ongoing feelings of guilt, sadness, and memory and cognition impairment. It is a multidimensional illness that affects many functionally integrated pathways of the brain. Understanding the underlying brain dysfunction that gives rise to this complex illness has been challenging, and by extension the search for appropriate treatments. MDD patients who are considered treatment resistant make up the primary population that receives electroconvulsive therapy (ECT). Remarkably, ECT shows a 75% remission rate in this patient population and is considered the “gold standard” treatment for major depression. Although the exact mechanism of its function is unknown, it is well accepted that the induced grand-mal seizure confers its therapeutic effect. The seizure likely has broad effect that somehow corrects the underlying dysfunction in brain circuitry. Here, we specifically examined studies of functional connectivity and metabolite changes. METHODS: Through literature search, we examined six studies in functional connectivity and four studies in magnetic resonance spectroscopy (MRS). RESULTS: Functional Connectivity: Studies have found that after bilateral ECT treatments, patients with major depression showed reduction of functional connectivity (FC) from the left dorsolateral prefrontal cortex (DLPFC) to other cortical and limbic structures. Correlated activity between the superior frontal gyri, middle frontal gyri and angular gyri were significantly increased after ECT. Hyperdeactivation of the orbitofrontal cortex to negative emotional stimuli in patients was decreased, and it was associated with improvement in depressive symptoms. Regional activity in the subgenual anterior cingulate cortex (sgACC) and functional connectivity between the sgACC and left hippocampus in treatment naïve patients after ECT were increased and correlated to reduction of depressive symptoms. Reduced connectivity between the amygdale and sgACC and increased connectivity between the amygdale and DLPFC was found by sequential assessments over a course of ECT treatments. Lastly, ECT increased the functional connectivity between DLPFC and the default mode network. MRS: Studies found decreased levels of glutamate or glx (glutamate/glutamine/ GABA) in patients in the anterior cingulate cortex and dorsolateral prefrontal cortex (DLPFC) compared to healthy controls. Additionally, it was found that glx levels increased after ECT treatments and that this increase was only in those who responded to treatment. Lastly, GABA level increased after ECT treatment in the occipital cortex. Discussion: Results from functional connectivity and brain metabolite studies in patients with major depression point to induced neuroplasticity as part of ECT’s therapeutic mechanism. Remodeling connectivity and mediating metabolite changes both will require modifications at the synaptic level. The wide spread changes seen in several different brain regions that have been implicated in depression further suggests that ECT’s effects are both highly specific and broad. CONCLUSION: Electroconvulsive therapy has consistently demonstrated impressive efficacy among the most severely depressed patients and is known to produce widely distributed effects in the brain. However, this also makes assessing its therapeutic mechanism challenging. Magnetic resonance imaging studies assessing functional connectivity and brain metabolite levels have demonstrated that ECT likely produces neuroplastic changes to remodel aberrant connectivity and dysfunctional excitatory and inhibitory neurotransmission in cortical and limbic areas. Although these findings should be interpreted with caution, this field of research has provided an unprecedented opportunity to examine the living brain in great detail. Further studies with larger sample sizes and improved technical specifications will likely yield greater results.

The problem of this investigation is twofold. First, to demonstrate the effects of the variation of convulsive-nonconvulsive electroshock treatment used in this study in relation to memory alteration in schizophrenia as measured by the Wechsler Memory Scale. Second, to determine those aspects of memory that are the most affected, and those that are the least affected by this form of treatment.

Reliable observation of ECT-induced hormone release requires that other processes that affect hormone levels remain constant and not obscure it. This article reviews principles and pitfalls in making such observations. Clinical applicability and limitations of measurements of prolactin, cortisol, oxytocin, in vasopressin, and other hormones are described. Applications, include elucidation of ECT physiology and seizure quality, comparison of ECT techniques, and description of illness severity. Accounting for each of these different effects can be needed to characterize any of them. An important but unrealized application of neuroendocrine measurement is prediction of the stability of individual ECT response.

No description available.

The purpose was to investigate some aspects of epidemiology, risk factors and treatment with ECT in advanced Parkinson’s disease (PD). In study I, we performed a descriptive epidemiologic population-based survey in the Central Health Care District in Östergötland in south-east Sweden, with a population of almost 150,000 inhabitants 1989. The case finding was accomplished in three ways: 1. Collection of all prescriptions for Parkinson’s disease. 2. Search in medical files. 3. Checking with all nursing homes in the area. The crude prevalence was found to be 115 per 100,000 inhabitants. When we used the European Standard Population as a tool for easy comparisons of PD prevalence between different areas and time periods 76 PD-cases per 100,000 inhabitants were found. The corresponding incidences were 11.0 (crude) and 7.9 (age standardised) per 100,000 person-years. Mean age at onset was 65.6. A low prevalence and a high age at onset suggested that e.g. environmental factors could influence the occurrence of PD, and the results implies that only few such factors were present in the investigated area. The findings led to study II, a case-control study which investigated the possible impact of nutritional and environmental risk factors for idiopathic Parkinson’s disease (IP), including 113 cases and 263 control subjects. Dietary, drinking, and smoking habits, as well as previous occupation, were requested in a structured questionnaire. No increased risk was found for any of the nutrients. A reduced risk was found for coffee, wine, and spirits but also for broiled meat, smoked ham or meat, eggs, French loaf or white bread, and tomatoes. These findings could indicate an antioxidant effect. Frequency of preceding and present smoking was reduced in IP patients. Possible mechanisms are discussed. Various occupational groups and exposures were analysed and increased risks of IP in men were found for agricultural work, pesticide exposure, male carpenters, and in female cleaners. In advanced PD there is a need for further therapeutic improvements, and electroconvulsive therapy (ECT) is one insufficiently explored and evaluated method. In study III ECT 16 non-depressed, nondemented PD patients with advanced disease were treated with ECT. In all patients an antiparkinsonian effect of ECT was seen, lasting between a few days and 18 months. Five patients, all with signs of blood brain barrier damage, developed transitory mental confusion after ECT. The results indicated that ECT could cause increased dopaminergic activity, which led us to study IV. Single photon emission computed tomography (SPECT) with the cocaine analogue [123I]-β-CIT was used in order to visualise dopaminergic neurones in the brain. Six patients with PD were examined before and after a series of ECT, and in three cases SPECT was also repeated after one year. The side-to-side difference in the radiotracer uptake was found to be significantly lower in striatum located contralaterally to the part of the body with most pronounced symptomatology. No significant change in uptake of [123I]-β-CIT was seen after ECT, although all patients improved and the most pronounced improvement was seen in patients with less advanced PD. Study V points at two new positive observations with maintenance ECT (MECT). i.e. repeated ECT treatment of PD. One patient had either severe mental side effects on higher L-dopa doses or intolerable parkinsonian symptoms on lower doses. MECT implied marked improvement in parkinsonian symptoms without mental side effects. Another PD patient, who also had a mental depression, showed slight improvement of motor symptoms on a series of ECT. When treated with MECT further antiparkinsonian effects were seen. / On the day of the public defence the status of the article IV was: Submitted; articel V was: Accepted for publication after revision.

No description available.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23076号 / 医博第4703号 / 新制||医||1049(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 花川 隆, 教授 古川 壽亮, 教授 髙橋 良輔 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

While the learned helplessness effect has been reliably found in dogs and other species (e.g., cats, mice, fish, and humans), it has been somewhat difficult to obtain in rats. In addition, it has been demonstrated that electroconvulsive shock (ECS) reverses learned helplessness in dogs, but ECS induced reversal has not been demonstrated in the rat. Thus, the purpose of this dissertation was twofold: (1) to determine if the learned helplessness effect could be reliably demonstrated in rats; and (2) if so, will a single ECS attenuate this phenomenon. If it could be shown that ECS attenuates helplessness, then two purposes would be served: (a) it would extend the generality of learned helplessness theory by indicating additional parallels between dog helplessness and rat helplessness; and (b) it would expand the parallels between learned helplessness and human depression, thereby increasing the validity of the learned helplessness model of depression. In Experiment 1, rats were randomly assigned to one of three groups: escape, yoked-inescapable, and no shock control. Each rat in the escape group received 80 trials of unsignaled escapable shock. The escape group rats were required to perform a progressive fixed-ratio bar press to escape shock. The yoked-inescapable group received exactly the same intensity, frequency, and duration of shock its escape partner received; but no response would escape shock. The no-shock control group received only pre-exposure to the training apparatus. The following day all rats were tested on a FR-2 shuttlebox escape/avoidance task. After test, half the rats in each group were given a single ECS and then were retested 24 hours later in the shuttlebox. The learned helplessness effect was clearly demonstrated during the test phase. In addition, a single ECS attenuated the learned helplessness effect in rats. In Experiment 2 rats were given training exactly as described in Experiment 1. Following training, one-third of the rats in the escape and yoked-inescapable groups were given a single ECS immediately, one-third were given a single ECS 23.5 hours later, and one-third received no treatment. In the no-shock control group one-third of the rats were given a single ECS 24 hours prior to test, one-third of the rats were given ECS 30 minutes prior to test, and one-third of the rats were not given ECS. Then, all rats were tested 24 hours following training. The test session was identical to the test session in Experiment 1. The learned helplessness effect was clearly demonstrated during test in the NO-ECS condition. In addition, it was demonstrated that ECS attenuates or reverses learned helplessness training when given immediately following training. Delayed ECS also reverses helplessness, but less dramatically than immediate ECS. In both experiments the criteria which characterize learned helplessness were matched: (1) Failure to initiate the escape response in the presence of shock; (2) failure to maintain escape behavior even after occasional escape response occur; and (3) that conditions 1 and 2 above are a result of inescapability and not a result of shock per se. In addition, since ECS attenuates helplessness, the generality of helplessness theory was extended to rats, and the validity of learned helplessness model of depression was strengthened. / Doctor of Philosophy

The response deficit following exposure to inescapable shock has been termed "learned helplessness." This experiment was designed (a) to determine whether learned helplessness following an inescapable footshock induction procedure extends to 48 hours, and (b) to test the hypothesis that electroconvulsive shock (ECS) reverses learned helplessness in rats. Subjects were tested for helplessness in a bar-press shock-escape task. Results indicated that helplessness was not present 48 hours after exposure to inescapable shock. A slight indication of helplessness was observed in the first 10 trials of the 60-trial task. In addition, ECS was shown to enhance performance in the test task; however, this facilitation effect was seen only in control animals that were not previously exposed to inescapable footshock.