Structural magnetic resonance imaging of bipolar disorder

Bipolar disorders are illnesses with recurring episodes of elevated or depressed mood. Although most affected individuals have periods when they are free of symptoms, they carry a life-long risk of relapse. The cause of the illness has not yet been established. During the last three decades, a growing number of brain imaging studies have shown differences in brain morphology between persons with a bipolar disorder and healthy controls, though the affected brain regions have varied greatly across studies. Too small sample sizes are likely one explanation of this variability. The aims of this thesis were to investigate i) differences in brain morphology between bipolar patients and healthy controls, ii) differences between subgroups of bipolar disorder, and iii) changes in brain morphology associated with illness progression. To these ends, we collected a large sample of bipolar disorder patients and examined their brains using magnetic resonance imaging. We then made analyses on group level. In Study 1, we analyzed differences in gray matter volume between persons with bipolar disorder and healthy controls. We found lower volume in the bilateral insula and medial prefrontal cortex in the bipolar group. We also found that these two regions covary in size. In Study 2, we examined if cortical volume, thickness, and surface area differ between patients with bipolar disorder I and II. We found that bipolar I subjects had thinner rostral temporal cortex than bipolar II subjects. Many patients with bipolar disorder experience psychotic symptoms during an illness episode. In Study 3, we investigated if gray matter volume differs between patients with a history of psychosis and those without. We found lower volume in the fusiform gyrus, dorsolateral prefrontal cortex, and inferior frontal cortex in the group of patients with previous psychosis. In Study 4, we analyzed if gray matter volume was associated with the lifetime number of manic or depressive episodes, or the duration of the illness in a group of patients with bipolar I disorder without comorbidity. We found a linear negative correlation between the volume of the dorsolateral prefrontal cortex and the lifetime number of manic episodes. This cross sectional analysis could, however, not establish if the volume reduction predates the manic episodes or is an effect of manic episodes. Therefore, we re-scanned the patients after six years. In study 5, we then compared those patients who had had at least one manic episode between baseline and follow-up with those who did not. We found that the volume in the dorsolateral and inferior frontal cortex decreased in the group who had had a manic episode. In summary, the studies suggest that bipolar disorder is associated with reduced gray matter volume in brain areas responsible for emotional regulation. We also found that the brain morphology differs between subgroups of bipolar disorder. Finally, our results suggest that manic episodes cause gray matter volume reduction in regions coupled to cognitive functions that tend to be impaired in bipolar disorder

Electroconvulsive Therapy in Depression: Improvement in Quality of Life Depending on Age and Sex

Objectives It is uncertain if there are variations in the improvement of quality in life between sexes and age groups after electroconvulsive therapy (ECT). The aim of this study was to investigate how health-related quality of life changed after treatment and to examine differences in the results between sex and age groups. Methods This register-based study used data from the Swedish national quality register for ECT. The study population was patients diagnosed with depression who had received ECT. Health-related quality of life was quantified using the 3-level version the EuroQol 5-dimensional questionnaire (EQ-5D 3 L). Analysis of variance was used to compare change in EQ-5D score from pretreatment to posttreatment between sex and age groups. Results There was a statistically significant improvement in EQ-5D index score and EQ visual analog scale (VAS) score in all patient groups after ECT. The mean improvement in EQ-5D index score and EQ-VAS score ranged from 0.31 to 0.46 and 28.29 to 39.79, respectively. Elderly patients had greater improvement in EQ-5D index score and EQ-VAS score than younger patients. There was no significant difference in improvement between the sexes. The mean improvement in EQ-5D index score was 0.40 for male patients and 0.41 for female patients. Conclusions Electroconvulsive therapy had a considerable effect on health-related quality of life in patients with depression of both sexes and all age groups. The improvement was greatest in elderly patients, who more often had psychotic features. More studies are needed to investigate the long-term effects of ECT and to further explain the varying treatment results between elderly and younger patients.publishedVersio

Validity of diagnoses, treatment dates, and rating scales in the Swedish national quality register for electroconvulsive therapy

Background The Swedish national quality register for electroconvulsive therapy (Q-ECT) contains data on patients receiving treatment with electroconvulsive therapy (ECT) in Sweden. Aim This study determined the validity of diagnoses, treatment dates, and rating scales in the Q-ECT by investigating the degree of accordance between data from the Q-ECT and patient records. Materials and methods From January 2016 to December 2017, 200 treatment series were randomly selected from the Q-ECT. The corresponding patient records were requested from the treating hospitals. Data on the indicative diagnosis, dates for the first and the last ECT session, and rating scales were compared between the Q-ECT and patient records using (i) a strict and (ii) a liberal method of assessment. Using the liberal method, each variable was assessed as accordant if it belonged to the same diagnosis group, or if the dates differed by less than 1 week, or ratings differed by only 1 point on the Clinical Global Impression Scale (CGI- S), or no more than 3 points on the Montgomery Åsberg Depression Rating Scale between the Q-ECT and the patient record. Results A total of 179 patient records were received. The strict method of assessment showed an accordance of 89% or higher for all studied variables. The liberal method showed an accordance of 95% or higher. Conclusions We conclude that data on the studied variables in the Q-ECT have high validity. However, limited use of some rating scales makes the results uncertain. Measures can be taken to further improve the data quality.publishedVersio

System Identification and Tuning of Wireless Power Transfer Systems with Multiple Magnetically Coupled Resonators

We present a procedure for system identification and tuning of a wireless power transfer (WPT) system with four magnetically coupled resonators, where each resonator consists of a coil and a capacitor bank. The system-identification procedure involves three main steps: 1) individual measurement of the capacitor banks in the system; 2) measurement of the frequency-dependent two-port impedance matrix of the magnetically coupled resonators; and 3) determining the inductance of all coils and their corresponding coupling coefficients using a Bayesian approach. The Bayesian approach involves solving an optimization problem where we minimize the mismatch between the measured and simulated impedance matrix together with a penalization term that incorporates information from a direct measurement procedure of the inductance and losses of the coils. This identification procedure yields an accurate system model which we use to tune the four capacitance values to recover high system-performance and account for, e.g., manufacturing tolerances and coil displacement. For a prototype WPT system, we achieve 3.3 kW power transfer with 91 % system efficiency over an air-gap distance of approximately 20 cm

A novel atlas of gene expression in human skeletal muscle reveals molecular changes associated with aging

Background: Although high-throughput studies of gene expression have generated large amounts of data, most of which is freely available in public archives, the use of this valuable resource is limited by computational complications and non-homogenous annotation. To address these issues, we have performed a complete re-annotation of public microarray data from human skeletal muscle biopsies and constructed a muscle expression compendium consisting of nearly 3000 samples. The created muscle compendium is a publicly available resource including all curated annotation. Using this data set, we aimed to elucidate the molecular mechanism of muscle aging and to describe how physical exercise may alleviate negative physiological effects. Results: We find 957 genes to be significantly associated with aging (p <0.05, FDR = 5 %, n = 361). Aging was associated with perturbation of many central metabolic pathways like mitochondrial function including reduced expression of genes in the ATP synthase, NADH dehydrogenase, cytochrome C reductase and oxidase complexes, as well as in glucose and pyruvate processing. Among the genes with the strongest association with aging were H3 histone, family 3B (H3F3B, p = 3.4 x 10(-13)), AHNAK nucleoprotein, desmoyokin (AHNAK, p = 6.9 x 10(-12)), and histone deacetylase 4 (HDAC4, p = 4.0 x 10(-9)). We also discover genes previously not linked to muscle aging and metabolism, such as fasciculation and elongation protein zeta 2 (FEZ2, p = 2.8 x 10(-8)). Out of the 957 genes associated with aging, 21 (p <0.001, false discovery rate = 5 %, n = 116) were also associated with maximal oxygen consumption (VO2MAX). Strikingly, 20 out of those 21 genes are regulated in opposite direction when comparing increasing age with increasing VO2MAX. Conclusions: These results support that mitochondrial dysfunction is a major age-related factor and also highlight the beneficial effects of maintaining a high physical capacity for prevention of age-related sarcopenia.Peer reviewe

Outcome of transcranial magnetic intermittent theta-burst stimulation in the treatment of depression-A Swedish register-based study

Background: Repetitive transcranial magnetic stimulation (rTMS) is an established treatment of depression. The more recently introduced intermittent Theta-burst stimulation (iTBS) has shown significant superiority over sham-stimulation and equal effect sizes to a 10 Hz protocol in one clinical trial. The aim of the current study was to investigate the effectiveness and tolerability of iTBS in a naturalistic, clinical setting. Further, we explored demographical and clinical predictors of response. Methods: Data was collected from seventeen rTMS-sites in Sweden between January 2018 and May 2021, through the Swedish National Quality register for repetitive Transcranial Magnetic Stimulation (Q-rTMS). We included 542 iTBS-treated patients with unipolar or bipolar depression. Outcome was assessed with Clinical Global Impression Severity and Improvement scores in an intention to treat analysis. Results: The response rate was 42.1 % and 16.1 % reached remission. The response rate was significantly larger in the oldest age group compared to the youngest (odds ratio 3.46, 95 % confidence interval 1.65-7.22). Less severe level of depression (Montgomery-Asberg depression rating scale self-assessment &lt; 36) at baseline predicted response and remission. Only &lt;1 % were much or very much worse after treatment. Drop-out rate was 10.9 %. No serious adverse events were reported. Limitations: Retrospective analysis of register data. No comparison group. Conclusions: In a clinical setting, iTBS was shown to be safe and tolerable and the response rate was similar to that reported from clinical trials. Older age-group and less severe illness predicted response

Electroconvulsive Therapy Versus Repetitive Transcranial Magnetic Stimulation in Patients With a Depressive Episode : A Register-Based Study

Objectives  Electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) are both effective in treating depression. Although rTMS induces fewer adverse effects, its effectiveness relative to ECT is not well established. The aim of this study was to investigate the treatment outcomes of ECT and rTMS in patients who have received both interventions. Methods  This was a register-based observational crossover study in patients with depression who had undergone ECT and rTMS in Sweden between 2012 and 2021. Primary outcome was reduction in the Montgomery-Åsberg Depression Rating Scale—Self-report (MADRS-S) score. Secondary outcome was response defined as a 50% or greater decrease in the MADRS-S score. Subgroup analyses were performed to identify factors that predicted differential responses between rTMS and ECT. Continuous and categorical variables were analyzed using paired-samples t tests and McNemar tests, respectively. Results  In total, 138 patients across 19 hospitals were included. The MADRS-S score after ECT and rTMS was reduced by 15.0 and 5.6 (P = 0.0001) points, respectively. Response rates to ECT and rTMS were 38% and 15% (P = 0.0001), respectively. Electroconvulsive therapy was superior across all subgroups classified according to age and severity of depression. Conclusions  Our results suggest that ECT is more effective than rTMS in treating depression among patients who have received both interventions. Age and baseline depression severity did not predict who would similarly benefit from rTMS and ECT

The Incidence of Dental Fracturing in Electroconvulsive Therapy in Sweden

Objectives  One adverse effect of electroconvulsive therapy (ECT) is dental fracture; thus, a bite guard and muscle relaxants are used to prevent it. Earlier research reported varying rates of dental fracture, but there is no large-scale study on the incidence of dental fracture during ECT. This study aimed to examine the incidence of dental fracture during ECT and to investigate whether the incidence differs between different sexes, age groups, diagnosis groups, electrode placements, or number of treatment sessions. Methods  This register-based study used data from the Swedish national quality register for ECT. All hospitals offering ECT report to this register, and the coverage ratio is about 90%. All registered patients who started an ECT series between January 2012 and January 2019 were included in this study, with the data representing 16,681 individuals, 38,862 series, and 254,906 sessions. Results  Forty-six dental fractures were identified, giving an incidence of dental fracture of 0.2% per series, 0.02% per session, and 0.3% per individual. We did not find any significant associations between dental fracture rates and male or female populations, age, or different diagnosis groups, nor was there any significant difference between dental fracture rates and electrode placement. The mean number of treatments was significantly higher in the dental fracture group than in patients without dental fracture. Conclusions  There is a minimal risk of dental fracture during ECT. Our findings, together with those of other studies, provide further motivation for the use of a bite guard and muscle relaxant

The incidence of dental fracturing in electroconvulsive therapy in Sweden

Objectives: One adverse effect of electroconvulsive therapy (ECT) is dental fracture; thus, a bite guard and muscle relaxants are used to prevent it. Earlier research reported varying rates of dental fracture, but there is no large-scale study on the incidence of dental fracture during ECT. This study aimed to examine the incidence of dental fracture during ECT and to investigate whether the incidence differs between different sexes, age groups, diagnosis groups, electrode placements, or number of treatment sessions. Methods: This register-based study used data from the Swedish national quality register for ECT. All hospitals offering ECT report to this register, and the coverage ratio is about 90%. All registered patients who started an ECT series between January 2012 and January 2019 were included in this study, with the data representing 16,681 individuals, 38,862 series, and 254,906 sessions. Results: Forty-six dental fractures were identified, giving an incidence of dental fracture of 0.2% per series, 0.02% per session, and 0.3% per individual. We did not find any significant associations between dental fracture rates and male or female populations, age, or different diagnosis groups, nor was there any significant difference between dental fracture rates and electrode placement. The mean number of treatments was significantly higher in the dental fracture group than in patients without dental fracture. Conclusions: There is a minimal risk of dental fracture during ECT. Our findings, together with those of other studies, provide further motivation for the use of a bite guard and muscle relaxant