Thesis (M.Sc. (Clinical Psychology)) --University of the North, 1981 / Refer to the document

Treatments such as electroconvulsive shock (ECS) impair later performance of learned responses if presented shortly after learning, but not if delayed for a sufficient time. These gradients are frequently termed retrograde amnesia and interpreted as reflecting a memory consolidation process. The present investigation was concerned with the relationship of the length of the gradient produced by a single ECS to the duration of the memory consolidation process. In the first experiment, rats were trained on a one-trial passive avoidance task and then presented with one of three ECS treatments. The treatments were five ECSs of 0.5 seconds duration spaced either 1 minute apart, 5 seconds apart, or in one continuous 2.5 second duration burst. The five ECSs spaced 1 minute apart were found to impair performance when presented immediately, 1 hour, 24 hours, and 48 hours but not 9 days after passive avoidance training. Five ECSs spaced 5 seconds apart impaired performance when presented immediately or 1 hour but not 24 hours after training. In contrast, the single 2.5 second duration ECS impaired performance when presented immediately but not 1 hour or longer after training. The impairments produced by the five ECSs spaced 1 minute apart at 1 hour and 24 hours were found to be permanent over 11 days. The second experiment examined whether the long gradient produced by five ECSs spaced 1 minute apart was qualitatively different from single ECS gradients. Five ECSs spaced 1 minute apart were presented following passive avoidance training to rats anesthetized with ether or sodium pentobarbital. In both cases, the series of ECSs still impaired performance when presented 1 or 24 hours but not 9 days following passive avoidance training. This finding does not provide support for a distinction between the gradients produced by a single ECS and a series of ECSs. These results were therefore interpreted as showing that the length of the gradient produced by a single ECS in a passive avoidance task is not a good estimate of the duration of time required for memory consolidation. In this passive avoidance task, consolidation appears to continue for a period of at least several days, while the gradient produced by a single ECS was less than 1 hour. In the third experiment, rats were trained on a one - trial appetitive taste and then presented with either five ECSs spaced 1 minute apart, or a single ECS of 0.5 seconds or 2.5 seconds duration. In contrast to the results in the passive avoidance task, the five ECSs paced 1 minute apart did not produce a longer gradient than a single ECS of either 0.5 or 2.5 seconds duration. All three treatments impaired performance when presented 15 seconds but not 1 hour after training. Several possible explanations for the different effects of the series of ECSs in the two tasks are considered, and it is concluded that this difference probably reflects differences between the memory consolidation processes in the two tasks. / Arts, Faculty of / Psychology, Department of / Graduate

Recent experimental evidence indicates that the effectiveness of posttraining electroconvulsive shock in disturbing retention is not constant but highly variable. One factor which appears to contribute to this variation is the strength of the electroshock current. Currents of higher intensity or of longer duration have generally been found to be more effective in disturbing retention. Indirectly, this evidence suggests that an electroshock treatment does not invariably stop memory consolidation. It appears that following a weak electroshock treatment, the interference with consolidation is not complete and that consolidation may continue afterwards. This possibility was directly examined in the present experiment with a one-trial passive avoidance task. The results showed that rats given one electroconvulsive shock 5 min after the passive avoidance training suffered only a slight loss of retention. However, when a second electroconvulsive shock was given at 1 hr after training, there was a significantly greater retention loss than that following one electroconvulsive shock at 5 min or at 1 hr. Additional results indicate that the disruptiveness of the second electroconvulsive shock is time-dependent and that the retention deficit does not appear to be due to punishing or disinhibitory effects of the electroconvulsive shocks. These findings are interpreted as indicating that memory consolidation can continue after electroconvulsive shock. / Arts, Faculty of / Psychology, Department of / Graduate

When periodic electroconvulsive shocks (ECSs) were administered, a progressive intensification of the motor seizure (MS) pattern occurred. This effect was observed when ECSs at either 15 or 75 mA were administered at 3-day, but not 1-hr intervals. The magnitude of the increase in severity of the MS pattern was a function of the number of ECSs which approached asymptote, in these experiments, at approximately ten ECSs. Periodic ECSs were also found to potentiate the alcohol withdrawal syndrome. In general, those conditions which were found to facilitate the kindling of MSs were the same as those which produced the potentiation of the alcohol withdrawal syndrome. Furthermore, this potentiation was found to persist up to 3 weeks after the last ECS under the conditions used in these experiments. Finally, the potentiation of the alcohol withdrawal syndrome occurred even after the MSs had been pharmacologically blocked. The results of these experiments were discussed in light of their implications to both basic and clinical research. / Arts, Faculty of / Psychology, Department of / Graduate

No description available.

Electroconvulsive therapy (ECT) is used worldwide to treat severe mental disorders. The most common mental disorder, and the third leading cause of disease burden in the world is depression. The clinical efficacy of ECT for severe depression is well-established. However, both the pathophysiology of depression and the mechanism of action of ECT remain elusive. The main aims of this thesis are to address the following issues: 1) the use and practice of ECT in Sweden has not been systematically evaluated since 1975, 2) cognitive side-effects (memory disturbances) are a major concern with ECT and 3) the mechanism of action of ECT remain elusive. The neurobiological aspects of ECT focus on two hypotheses. First, the recent years´ preclinical studies that have provided evidence that ECT induces hippocampal cell proliferation, including neurogenesis. Second, that enhanced functional inhibition of neuronal activity is a key feature. Current use and practice of ECT in Sweden (paper I) is based on data from the national quality register for ECT, the mandatory patient register of the National Board of Health and Welfare and a survey. Treated person rate (TPR) in Sweden 2013 was found to be 41 individuals / 100 000, and thus unchanged since the latest systematic investigation in Sweden 1975. In more than 70% of treatment series the indication was a depressive episode. The selection of patients for ECT and treatment technique in Sweden was similar to that in other western countries, but the consent procedure and the involvement of nurses and nursing assistants in the delivery of ECT differ. Data also shows that there is room for improvement in both the specificity of use and availability of ECT. The second study in this thesis is a longitudinal observational trial where 12 (paper II and III) and 14 (paper IV) patients with depression referred for ECT were investigated. Patients underwent a 3 T MRI structural scanning and DSC-MRI perfusion, a neuropsychological test battery and clinical ratings before ECT, within one to two weeks after ECT and after 6 and 12 months.  In line with preclinical findings and the plasticity hypothesis of mechanism of action of ECT, the hippocampal volume increased after ECT in patients with depression. However, this increase was transient and returned to baseline levels within 6 months. No correlation was found between volumetric changes and clinical effect or cognitive outcome. Instead our results suggested an association to the number of treatments, without relation to the side of stimulation. A right-sided decrease in frontal blood flow distinguished remission from non-remission after ECT. There were significant impairments in verbal episodic memory and verbal fluency within one week after ending the ECT course, but these impairments were transient and no persistent cognitive impairments were seen during the follow-up. In summary, this thesis present the first update on the use and practice of ECT in Sweden in the last 40 years as well as a pioneering MRI-study on the hippocampal volume increase in the treatment of depression with ECT. Supportive to earlier findings we also found the cognitive side-effects that are measurable after ECT to be transient. Furthermore, we found that a decreased frontal blood flow is of importance for the anti-depressive response to ECT.

Conventional treatments for depression, such as pharmacological interventions, are often ineffective. Up to half of patients do not respond, resulting in a poor prognosis for depression. Therefore, treatment options can be invaluable for increasing rates of remission. It is generally assumed that aerobic exercise benefits affective state. However, exercise remains a controversial treatment, possibly due to inconsistent evidence and unknown mechanisms. It is hypothesised variable results (literature is conflicting) are due to/because of heterogeneity in exercise interventions and subjective reports of exercise and mood state. If a biomarker for depression can be identified, the effects of exercise on depression could be objectively assessed. Neuroimaging research has elucidated numerous biomarkers, but has had little benefit on the diagnosis, prognosis or treatment of depression. However, if research can identify which biomarkers respond to treatments, can stratify patients and which can predict response outcome, targets for new interventions can be developed. Therefore, this thesis first establishes the effect of ECT treatment on emotionally salient brain regions in MDD, establishing the basis of a treatment responsive biomarker and potential targets for other interventions. The same functional connectivity methods are then used to analyse the effects of a single bout of aerobic exercise in a healthy population. Similar reductions in functional connectivity were observed in brain structures relevant to depression, suggesting exercise might target relevant brain structures. Finally, using the same functional connectivity methods, a long-term aerobic exercise intervention is shown to reduce functional hyperconnectivity in mildly depressed participants compared to healthy controls. This supports two primary hypotheses: that hyperconnectivity may underlie depressive disorders, constituting a biomarker for depression; and that aerobic exercise is an effective treatment for milder forms of depression.

No description available.

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.