Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression.

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this causal depression network (CDN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis Principal Component Analysis (PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CDN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CDN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes (t = -2.35, p = 0.019). This evidence further supports that treatment interventions converge on a CDN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.

Exploring New Electroencephalogram Parameters in Electroconvulsive Therapy.

OBJECTIVE: This pilot study aims to evaluate a novel metric based on the power spectrum of the EEG recordings from ECT-induced seizures-its association to volume changes in the hippocampus after ECT and improvement in depression rating scores. METHODS: Depressed patients treated with ECT underwent brain magnetic resonance imaging before and after treatment and the EEG from each seizure was recorded (N = 29). Hippocampal volume changes and EEG parameters were recorded in addition to clinician-rated and self-reported measures of depressive symptoms. The slope of the power law in the power spectral density of the EEG was calculated. Multivariate linear models relating seizure parameters to volume change or clinical outcome were systematically and successively simplified. The best models were selected according to Akaike information criterion. RESULTS: The slope of the power law was steeper in the right than the left hemisphere (P < 0.001). Electroencephalogram measures were included in the best models of volume change for both hippocampi as well as in the models explaining clinical outcome ( P = 0.014, P = 0.004). CONCLUSIONS: In this pilot study, novel EEG measures were explored and contributed in models explaining the variation in volume change in the hippocampus and in clinical outcome after ECT.

Neurobiological mechanisms of ECT and TMS treatment in depression: study protocol of a multimodal magnetic resonance investigation.

BACKGROUND: Noninvasive neurostimulation treatments are increasingly being used to treat major depression, which is a common cause of disability worldwide. While electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) are both effective in treating depressive episodes, their mechanisms of action are, however, not completely understood. ECT is given under general anesthesia, where an electrical pulse is administered through electrodes placed on the patient's head to trigger a seizure. ECT is used for the most severe cases of depression and is usually not prescribed before other options have failed. With TMS, brain stimulation is achieved through rapidly changing magnetic fields that induce electric currents underneath a ferromagnetic coil. Its efficacy in depressive episodes has been well documented. This project aims to identify the neurobiological underpinnings of both the effects and side effects of the neurostimulation techniques ECT and TMS. METHODS: The study will utilize a pre-post case control longitudinal design. The sample will consist of 150 subjects: 100 patients (bipolar and major depressive disorder) who are treated with either ECT (N = 50) or TMS (N = 50) and matched healthy controls (N = 50) not receiving any treatment. All participants will undergo multimodal magnetic resonance imaging (MRI) as well as neuropsychological and clinical assessments at multiple time points before, during and after treatment. Arterial spin labeling MRI at baseline will be used to test whether brain perfusion can predict outcomes. Signs of brain disruption, potentiation and rewiring will be explored with resting-state functional MRI, magnetic resonance spectroscopy and multishell diffusion weighted imaging (DWI). Clinical outcome will be measured by clinician assessed and patient reported outcome measures. Memory-related side effects will be investigated, and specific tests of spatial navigation to test hippocampal function will be administered both before and after treatment. Blood samples will be stored in a biobank for future analyses. The observation time is 6 months. Data will be explored in light of the recently proposed disrupt, potentiate and rewire (DPR) hypothesis. DISCUSSION: The study will contribute data and novel analyses important for our understanding of neurostimulation as well as for the development of enhanced and more personalized treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05135897.

Intestinal barrier integrity in anorexia nervosa (a pilot study).

OBJECTIVE: There is no conclusive evidence for involvement of intestinal barrier alteration in the etiology of anorexia nervosa (AN). The aims of this pilot study were to identify serum markers of intestinal barrier integrity in patients with AN and to determine the relationships between those markers and body mass index (BMI), eating disorder symptoms, gastrointestinal complaints, and liver synthesis function (international normalized ratio [INR]). METHOD: Twenty-five outpatients with AN prior to starting treatment and 28 healthy controls (HC) were assessed. BMI and serum markers of intestinal barrier integrity were measured, including zonulin family peptides (ZFP), lipopolysaccharide-binding protein (LBP), and intestinal fatty-acid-binding protein (i-FABP). Eating disorder symptoms and gastrointestinal complaints were evaluated via questionnaires. RESULTS: The serum ZFP concentration was significantly lower in patients with AN than in HC (44.2 [7.4] vs. 49.2 [5.6] ng/ml, mean [standard deviation], p = .008). LBP and i-FABP did not differ between the two groups. In patients with AN, serum ZFP was significantly predicted by BMI (ß = 0.479, p = .009), age (ß = 0.411, p = .020), and INR (ß = -0.388, p = .028). No such associations were found for either gastrointestinal complaints or eating disorder symptoms. DISCUSSION: Abnormal levels of serum ZFP were observed in patients with AN. Further studies with other assessment methods are warranted to examine intestinal barrier function in AN. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02745067.

Elevated body weight modulates subcortical volume change and associated clinical response following electroconvulsive therapy.

Background: Obesity is a frequent somatic comorbidity of major depression, and it has been associated with worse clinical outcomes and brain structural abnormalities. Converging evidence suggests that electroconvulsive therapy (ECT) induces both clinical improvements and increased subcortical grey matter volume in patients with depression. However, it remains unknown whether increased body weight modulates the clinical response and structural neuroplasticity that occur with ECT. Methods: To address this question, we conducted a longitudinal investigation of structural MRI data from the Global ECT-MRI Research Collaboration (GEMRIC) in 223 patients who were experiencing a major depressive episode (10 scanning sites). Structural MRI data were acquired before and after ECT, and we assessed change in subcortical grey matter volume using FreeSurfer and Quarc. Results: Higher body mass index (BMI) was associated with a significantly lower increase in subcortical grey matter volume following ECT. We observed significant negative associations between BMI and change in subcortical grey matter volume, with pronounced effects in the thalamus and putamen, where obese participants showed increases in grey matter volume that were 43.3% and 49.6%, respectively, of the increases found in participants with normal weight. As well, BMI significantly moderated the association between subcortical grey matter volume change and clinical response to ECT. We observed no significant association between BMI and clinical response to ECT. Limitations: Because only baseline BMI values were available, we were unable to study BMI changes during ECT and their potential association with clinical and grey matter volume change. Conclusion: Future studies should take into account the relevance of body weight as a modulator of structural neuroplasticity during ECT treatment and aim to further explore the functional relevance of this novel finding.

International Consortium on the Genetics of Electroconvulsive Therapy and Severe Depressive Disorders (Gen-ECT-ic).

Recent genome-wide association studies have demonstrated that the genetic burden associated with depression correlates with depression severity. Therefore, conducting genetic studies of patients at the most severe end of the depressive disorder spectrum, those with treatment-resistant depression and who are prescribed electroconvulsive therapy (ECT), could lead to a better understanding of the genetic underpinnings of depression. Despite ECT being one of the most effective forms of treatment for severe depressive disorders, it is usually placed at the end of treatment algorithms of current guidelines. This is perhaps because ECT has controlled risk and logistical demands including use of general anaesthesia and muscle relaxants and side-effects such as short-term memory impairment. Better understanding of the genetics and biology of ECT response and of cognitive side-effects could lead to more personalized treatment decisions. To enhance the understanding of the genomics of severe depression and ECT response, researchers and ECT providers from around the world and from various depression or ECT networks, but not limited to, such as the Psychiatric Genomics Consortium, the Clinical Alliance and Research in ECT, and the National Network of Depression Centers have formed the Genetics of ECT International Consortium (Gen-ECT-ic). Gen-ECT-ic will organize the largest clinical and genetic collection to date to study the genomics of severe depressive disorders and response to ECT, aiming for 30,000 patients worldwide using a GWAS approach. At this stage it will be the largest genomic study on treatment response in depression. Retrospective data abstraction and prospective data collection will be facilitated by a uniform data collection approach that is flexible and will incorporate data from many clinical practices. Gen-ECT-ic invites all ECT providers and researchers to join its efforts.

Association between gastrointestinal complaints and psychopathology in patients with anorexia nervosa.

OBJECTIVE: Gastrointestinal (GI) symptoms appear frequently in patients with anorexia nervosa (AN), but the associations between psychopathological, GI, and eating disorder (ED) symptoms remain unclear. This study aimed to determine the relationships of GI complaints with psychopathological measures, ED symptoms, and body mass index (BMI) in patients with AN. METHOD: Thirty outpatients with AN aged >16 years were included. Psychopathological measures (Symptom Checklist-90-Revised, Beck Depression Inventory-II, and Beck Anxiety Inventory), ED symptoms (Eating Disorder Examination Questionnaire), ED-associated impairment (Clinical Impairment Assessment Questionnaire), GI complaints (Irritable Bowel Syndrome Severity Scoring System [IBS-SSS]), and BMI were assessed prior to starting treatment, and correlation and multiple regression analyses were applied to data from 19 patients. RESULTS: IBS-symptoms were significantly correlated only with ED symptoms (r = 0.583, p = .009) and somatization (r = 0.666, p = .002). Multiple regression analysis revealed that somatization significantly predicted worse IBS symptoms (beta = 0.5, p = .04), while ED symptoms did not. DISCUSSION: Higher IBS-SSS scores were associated with higher severities of other somatic complaints. GI complaints and somatization should be addressed in treatments for AN in order to prevent these factors impeding the establishment of healthy eating patterns. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02745067.

Right unilateral electroconvulsive therapy does not cause more cognitive impairment than pharmacologic treatment in treatment-resistant bipolar depression: A 6-month randomized controlled trial follow-up study.

OBJECTIVES: Electroconvulsive therapy is an effective treatment for bipolar depression, but there are concerns about whether it causes long-term neurocognitive impairment. METHODS: In this multicenter randomized controlled trial, in-patients with treatment-resistant bipolar depression were randomized to either algorithm-based pharmacologic treatment or right unilateral electroconvulsive therapy. After the 6-week treatment period, all of the patients received maintenance pharmacotherapy as recommended by their clinician guided by a relevant treatment algorithm. Patients were assessed at baseline and at 6 months. Neurocognitive functions were assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, and autobiographical memory consistency was assessed using the Autobiographical Memory Interview-Short Form. RESULTS: Seventy-three patients entered the trial, of whom 51 and 26 completed neurocognitive assessments at baseline and 6 months, respectively. The MATRICS Consensus Cognitive Battery composite score improved by 4.1 points in both groups (P = .042) from baseline to 6 months (from 40.8 to 44.9 and from 41.9 to 46.0 in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively). The Autobiographical Memory Interview-Short Form consistency scores were reduced in both groups (72.3% vs 64.3% in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively; P = .085). CONCLUSIONS: This study did not find that right unilateral electroconvulsive therapy caused long-term impairment in neurocognitive functions compared to algorithm-based pharmacologic treatment in bipolar depression as measured using standard neuropsychological tests, but due to the low number of patients in the study the results should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00664976.

Effectiveness of enhanced cognitive behavioral therapy (CBT-E) in the treatment of anorexia nervosa: a prospective multidisciplinary study.

BACKGROUND: Anorexia nervosa (AN) is a debilitating psychiatric disorder associated with a wide array of negative health complications and psychiatric comorbidity. Existing evidence for AN treatment in adults is weak, and no empirically supported treatment has been reliably established. The primary objective of this study is to gain knowledge about the effectiveness of enhanced cognitive behavioral therapy (CBT-E) for anorexia nervosa delivered in a public hospital setting. Baseline predictors of treatment outcome and dropout are studied. Furthermore, there will be collected blood and stool samples for a general biobank to be able to initiate research on possible pathophysiological mechanisms underlying AN. METHODS: The study will assess the potency of outpatient CBT-E in a sample of patients suffering from AN (age >16) admitted to the Section for Eating Disorders at the Department for Psychosomatic Medicine, Haukeland University Hospital in Bergen, Norway. The study has a longitudinal design with five main assessment time points: before treatment, at 3 months, at the end of treatment, at 20 weeks, and at 12 months follow-up including biobank samples. A control group without an eating disorder will also be recruited. DISCUSSION: Treatment research in a public hospital setting is important for gaining knowledge about the transportability of treatments evaluated in research clinics into ordinary clinical practice. Furthermore, biological material from the thoroughly described patient cohort will serve as a basis for further research on the pathophysiological mechanisms in AN. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02745067 . Registered 14 April 2016. .

Effects of ECT in treatment of depression: study protocol for a prospective neuroradiological study of acute and longitudinal effects on brain structure and function.

BACKGROUND: Major depression can be a serious and debilitating condition. For some patients in a treatment resistant depressive episode, electroconvulsive treatment (ECT) is the only treatment that is effective. Although ECT has shown efficacy in randomized controlled trials, the treatment is still controversial and stigmatized. This can in part be attributed to our lack of knowledge of the mechanisms of action. Some reports also suggest potential harmful effects of ECT treatment and memory related side effects have been documented. METHODS/DESIGN: The present study will apply state of the art radiology through advanced magnetic resonance imaging (MRI) techniques to investigate structural and functional brain effects of ECT. As a multi-disciplinary collaboration, imaging findings will be correlated to psychiatric response parameters, neuropsychological functioning as well as neurochemical and genetic biomarkers that can elucidate the underlying mechanisms. The aim is to document both treatment effects and potential harmful effects of ECT. SAMPLE: n = 40 patients in a major depressive episode (bipolar and major depressive disorder). Two control groups with n = 15 in each group: age and gender matched healthy volunteers not receiving ECT and patients undergoing electrical cardioversion (ECV) for atrial fibrillation (AF). Observation time: six months. DISCUSSION: The study will contribute to our understanding of the pathophysiology of major depression as well as mechanisms of action for the most effective treatment for the disorder; ECT.

Unmasking patient diversity: Exploring cognitive and antidepressive effects of electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is an established treatment for depression, but more data on effectiveness and safety in clinical practice is needed. The aim of this register-based study was to investigate short-term effectiveness and cognitive safety after ECT, evaluated by clinicians and patients. Secondary, we investigated predictors for remission and cognitive decline. METHODS: The study included 392 patients from the Regional Register for Neurostimulation Treatment in Western Norway. Depressive symptoms and cognitive function were assessed with Montgomery-Åsberg Depression Rating Scale and Mini-Mental State Examination (clinician-rated) and Beck Depression Inventory and Everyday Memory Questionnaire (patient-rated). Assessments were done prior to ECT-series and a mean of 1.7 days after (range 6 days before and 12 days after) end of ECT-series. Paired samples t-tests were extended by detailed, clinically relevant subgroups. Predictors were examined using logistic regression. RESULTS: Clinician- and patient-rated remission rates were 49.5 and 41.0%, respectively. There was a large reduction in depressive symptoms and a small improvement in cognition after ECT, but we also identified subgroups with non-response of ECT in combination with cognitive decline (4.6% clinician-rated, 15.7% patient-rated). Positive predictors for patient- and clinician-rated remission were increasing age, shorter duration of depressive episode, and psychotic features. Antipsychotic medication at the commencement of treatment and previous ECT-treatment gave higher odds of clinician-rated remission, whereas higher pretreatment subjective depression level was associated with lower odds for patient-rated remission. Clinician-rated cognitive decline was predicted by higher pretreatment MMSE scores, whereas psychotic features, increasing age, and greater pretreatment subjective memory concerns were associated with lower odds for patient-rated cognitive decline. CONCLUSIONS: Our study supports ECT as an effective and safe treatment, although subgroups have a less favorable outcome. ECT should be considered at an early stage for older patients suffering from depression with psychotic features. Providing comprehensive and balanced information from clinicians and patients perspectives on effects and side effects, may assist in a joint consent process.

Neurocognitive profiles in treatment-resistant bipolar I and bipolar II disorder depression.

BACKGROUND: The literature on the neuropsychological profiles in Bipolar disorder (BD) depression is sparse. The aims of the study were to assess the neurocognitive profiles in treatment-resistant, acutely admitted BD depression inpatients, to compare the neurocognitive functioning in patients with BD I and II, and to identify the demographic and clinical illness characteristics associated with cognitive functioning. METHODS: Acutely admitted BD I (n = 19) and BD II (n = 32) inpatients who fulfilled the DSM-IV-TR criteria for a major depressive episode were tested with the MATRICS Consensus Cognitive Battery (MCCB), the Wechsler Abbreviated Scale of Intelligence, the National Adult Reading Test, and a battery of clinical measures. RESULTS: Neurocognitive impairments were evident in the BD I and BD II depression inpatients within all MCCB domains. The numerical scores on all MCCB-measures were lower in the BD I group than in the BD II group, with a significant difference on one of the measures, category fluency. 68.4% of the BD I patients had clinically significant impairment (>1.5 SD below normal mean) in two or more domains compared to 37.5% of the BD II patients (p = 0.045). A significant reduction in IQ from the premorbid to the current level was seen in BD I but not BD II patients. Higher age was associated with greater neurocognitive deficits compared to age-adjusted published norms. CONCLUSIONS: A high proportion of patients with therapy-resistant BD I or II depression exhibited global neurocognitive impairments with clinically significant severity. The cognitive impairments were more common in BD I compared to BD II patients, particularly processing speed. These findings suggest that clinicians should be aware of the severe neurocognitive dysfunction in treatment-resistant bipolar depression, particularly in BD I. TRIAL REGISTRATION: NCT00664976.

Differences in sleep patterns between patients with anorexia nervosa and healthy controls: a cross-sectional study.

BACKGROUND: Sleep difficulties are common in patients with anorexia nervosa (AN), but objective assessments have mostly been performed in hospital and laboratory settings. We aimed to identify differences in sleep patterns between patients with AN and healthy controls (HC) in their free-living environments, and potential associations between sleep patterns and clinical symptoms in patients with AN. METHODS: This cross-sectional study analyzed 20 patients with AN prior to them starting outpatient treatment and 23 HC. Sleep patterns were measured objectively using an accelerometer (Philips Actiwatch 2) for 7 consecutive days. Average sleep onset, sleep offset, total sleep time, sleep efficiency, wake after sleep onset (WASO) and mid-sleep awakenings lasting ≥ 5 min were compared between patients with AN and HC using nonparametric statistical analyses. Associations of sleep patterns with body mass index, eating-disorder symptoms, eating-disorder-associated impairment, and symptoms of depression were assessed in the patient group. RESULTS: Compared with HC, patients with AN had shorter WASO [median (interquartile range(IQR)): 33 vs. 42 min], but a longer average duration of mid-sleep awakenings lasting ≥ 5 min [median (IQR): 9 vs. 6 min, p = 0.006] and had more nights with no sleep (six nights in four patients with AN vs. zero nights in HC). There were no differences between patients with AN and HC regarding other sleep parameters and no significant correlations between sleep patterns and clinical parameters in patients with AN. However, HC presented a Intraindividual variability pattern that was closer to a normal distribution, whereas patients with AN tended to either have very regular or large variability in sleep onset time (AN; n = 7 < 25th percentile and n = 8 > 75th percentile vs. HC; n = 4 < 25 percentile and n = 3 > 75th percentile) during the week of sleep recordings. CONCLUSION: Patients with AN seem to spend more time awake during the night and have more nights without sleep than do HC, even though their average weekly sleep duration did not differ from that in HC. The intraindividual variability in sleep pattern seems to be an important parameter that should be assessed when studying sleep in patients with AN. Trial registration ClinicalTroals.gov. Identifier: NCT02745067. Registered: April 20, 2016.

Sleep disturbances are common in patients with anorexia nervosa. However, most studies that have assessed sleep patterns in this patient group have used either sleep questionnaires or sleep-measuring instruments in surroundings different from where they usually sleep. This study compared sleep patterns between patients with anorexia nervosa and healthy individuals without an eating disorder in their home environments using an accelerometer over 1 week. The accelerometer used was a sleep-monitoring instrument that looks similar to a wristwatch and records sleep patterns using movement and light sensors, and is easy to use in the home environment. We observed that patients with anorexia nervosa on average had longer periods awake during the night, as well as more awake nights compared with healthy individuals. Nevertheless, the average sleep duration during the week of sleep recordings was similar in the two groups. However, we also observed considerable variations in sleep patterns among the patients with anorexia nervosa, ranging from very regular to very irregular sleep patterns. We therefore believe that variability in the sleep patterns among patients with anorexia nervosa is an important parameter that should be included when studying sleep in these patients.

Electroconvulsive therapy triggers a reversible decrease in brain N-acetylaspartate.

Introduction: Based on previous research on electroconvulsive therapy (ECT) we have proposed a model where disruption, potentiation, and rewiring of brain networks occur in sequence and serve as the underlying therapeutic mechanism of ECT. This model implies that a temporary disturbance of neuronal networks (disruption) is followed by a trophic effect (potentiation), which enables the rewiring of neuronal circuits to a more euthymic functioning brain. We hypothesized that disruption of neuronal networks could trigger biochemical alterations leading to a temporary decrease in N-acetylaspartate (tNAA, considered a marker of neuronal integrity), while choline (a membrane component), myo-Inositol (mI, astroglia marker), and glutamate/glutamine (Glx, excitatory neurotransmitter) were postulated to increase. Previous magnetic resonance spectroscopy studies, reporting diverse findings, have used two different referencing methods - creatine ratios and tissue corrected values referenced to water - for the quantification of brain metabolites. Changes in creatine during ECT have also been reported, which may confound estimates adopting this as an internal reference. Methods: Using MR spectroscopy, we investigated 31 moderately to severely depressed patients and 19 healthy controls before, during, and after ECT or at similar time points (for controls). We tested whether biochemical alterations in tNAA, choline, mI, and Glx lend support to the disrupt, potentiate, and rewire hypothesis. We used both creatine ratios and water-scaled values for the quantification of brain metabolites to validate the results across referencing methods. Results: Levels of tNAA in the anterior cingulate cortex decreased after an ECT treatment series (average 10.6 sessions) by 6% (p = 0.007, creatine ratio) and 3% (p = 0.02, water referenced) but returned to baseline 6 months after ECT. Compared to after treatment series tNAA levels at 6-month follow-up had increased in both creatine ratio (+6%, p < 0.001) and water referenced data (+7%, p < 0.001). Findings for other brain metabolites varied and could not be validated across referencing methods. Discussion: Our findings suggest that prior research must be interpreted with care, as several referencing and processing methods have been used in the past. Yet, the results for tNAA were robust across quantification methods and concur with relevant parts of the disrupt, potentiate, and rewire model.

Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression.

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this common causal network (CCN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis (Principal Component Analysis, PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CCN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CCN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes. This evidence further supports that treatment interventions converge on a CCN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.

Experiences when implementing enhanced cognitive behavioral therapy as a standard treatment for anorexia nervosa in outpatients at a public specialized eating-disorder treatment unit.

BACKGROUND: Enhanced cognitive behavioral therapy (CBT-E) is a promising treatment option for outpatients with anorexia nervosa (AN). We aimed to determine the effectiveness of CBT-E as a standard treatment for adult outpatients with AN from the specialized eating-disorder unit of a public hospital with responsibilities to their catchment area. METHODS: This study had an open, longitudinal design. Thirty three (of planned 100) outpatients aged > 16 years suffering from AN were included to receive 40 sessions of CBT-E. Eating-disorder psychopathology and body mass index (BMI) were assessed before and after treatment, while comorbid psychiatric symptoms and trauma experiences were evaluated at the baseline, and therapeutic alliance was assessed after 4 weeks of treatment. RESULTS: A high proportion (69%) of patients dropped out of the treatment. Patient recovery was considered when they reached BMI > 18.5 and Eating Disorder Examination Questionnaire (EDE-Q) score < 2.5, and 27% of all patients recovered. CONCLUSIONS: Patients who completed the treatment had mostly satisfactory outcomes. Considering the high dropout rate, it is necessary to improve the strategies for engaging patients in therapy. Several aspects of CBT-E as a standard treatment are discussed regarding the high dropout rate. Trial registration ClinicalTrials.gov. Identifier: NCT02745067. Registered: April 20, 2016. https://clinicaltrials.gov/ct2/showNCT02745067.

Anorexia nervosa (AN) is difficult to treat, and no specific treatment approach has been demonstrated to be superior for adult outpatients. However, outcome data indicate that enhanced cognitive behavioral therapy (CBT-E) is a viable and promising treatment option for adults with AN, and its efficacy has been indicated in cohort studies and randomized controlled trials. The present study aimed to determine the effectiveness of CBT-E as a standard treatment for adult outpatients with AN from the specialized eating-disorder unit of a public hospital with responsibilities to their catchment area. Outpatient CBT-E was administered to 33 patients in a course of 40 sessions. Although 27% of the included patients had satisfactory treatment outcomes (healthy weights and reduced eating-disorder symptoms), more than two-thirds of all patients terminated treatment early. Several aspects of CBT-E as a standard treatment are discussed regarding this high dropout rate.

The Neurobiological Effects of Electroconvulsive Therapy Studied Through Magnetic Resonance: What Have We Learned, and Where Do We Go?

Electroconvulsive therapy (ECT) is an established treatment choice for severe, treatment-resistant depression, yet its mechanisms of action remain elusive. Magnetic resonance imaging (MRI) of the human brain before and after treatment has been crucial to aid our comprehension of the ECT neurobiological effects. However, to date, a majority of MRI studies have been underpowered and have used heterogeneous patient samples as well as different methodological approaches, altogether causing mixed results and poor clinical translation. Hence, an association between MRI markers and therapeutic response remains to be established. Recently, the availability of large datasets through a global collaboration has provided the statistical power needed to characterize whole-brain structural and functional brain changes after ECT. In addition, MRI technological developments allow new aspects of brain function and structure to be investigated. Finally, more recent studies have also investigated immediate and long-term effects of ECT, which may aid in the separation of the therapeutically relevant effects from epiphenomena. The goal of this review is to outline MRI studies (T1, diffusion-weighted imaging, proton magnetic resonance spectroscopy) of ECT in depression to advance our understanding of the ECT neurobiological effects. Based on the reviewed literature, we suggest a model whereby the neurobiological effects can be understood within a framework of disruption, neuroplasticity, and rewiring of neural circuits. An improved characterization of the neurobiological effects of ECT may increase our understanding of ECT's therapeutic effects, ultimately leading to improved patient care.

Changes in Tryptophan-Kynurenine Metabolism in Patients with Depression Undergoing ECT-A Systematic Review.

The kynurenine pathway of tryptophan (Trp) metabolism generates multiple biologically active metabolites (kynurenines) that have been implicated in neuropsychiatric disorders. It has been suggested that modulation of kynurenine metabolism could be involved in the therapeutic effect of electroconvulsive therapy (ECT). We performed a systematic review with aims of summarizing changes in Trp and/or kynurenines after ECT and assessing methodological issues. The inclusion criterium was measures of Trp and/or kynurenines before and after ECT. Animal studies and studies using Trp administration or Trp depletion were excluded. Embase, MEDLINE, PsycInfo and PubMed were searched, most recently in July 2022. Outcomes were levels of Trp, kynurenines and ratios before and after ECT. Data on factors affecting Trp metabolism and ECT were collected for interpretation and discussion of the reported changes. We included 17 studies with repeated measures for a total of 386 patients and 27 controls. Synthesis using vote counting based on the direction of effect found no evidence of effect of ECT on any outcome variable. There were considerable variations in design, patient characteristics and reported items. We suggest that future studies should include larger samples, assess important covariates and determine between- and within-subject variability. PROSPERO (CRD42020187003).

Neural Substrates of Psychotic Depression: Findings From the Global ECT-MRI Research Collaboration.

Psychotic major depression (PMD) is hypothesized to be a distinct clinical entity from nonpsychotic major depression (NPMD). However, neurobiological evidence supporting this notion is scarce. The aim of this study is to identify gray matter volume (GMV) differences between PMD and NPMD and their longitudinal change following electroconvulsive therapy (ECT). Structural magnetic resonance imaging (MRI) data from 8 independent sites in the Global ECT-MRI Research Collaboration (GEMRIC) database (n = 108; 56 PMD and 52 NPMD; mean age 71.7 in PMD and 70.2 in NPMD) were analyzed. All participants underwent MRI before and after ECT. First, cross-sectional whole-brain voxel-wise GMV comparisons between PMD and NPMD were conducted at both time points. Second, in a flexible factorial model, a main effect of time and a group-by-time interaction were examined to identify longitudinal effects of ECT on GMV and longitudinal differential effects of ECT between PMD and NPMD, respectively. Compared with NPMD, PMD showed lower GMV in the prefrontal, temporal and parietal cortex before ECT; PMD showed lower GMV in the medial prefrontal cortex (MPFC) after ECT. Although there was a significant main effect of time on GMV in several brain regions in both PMD and NPMD, there was no significant group-by-time interaction. Lower GMV in the MPFC was consistently identified in PMD, suggesting this may be a trait-like neural substrate of PMD. Longitudinal effect of ECT on GMV may not explain superior ECT response in PMD, and further investigation is needed.