This study aims to compare the effectiveness of EEG frequency band activity including interhemispheric asymmetry and prefrontal theta cordance in predicting response to escitalopram therapy at ...8-weeks post-treatment, in a multi-site initiative.
Resting state 64-channel EEG data were recorded from 44 patients with a diagnosis of major depressive disorder (MDD) as part of a larger, multisite discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). Clinical response was measured at 8-weeks post-treatment as change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) score of 50% or more. EEG measures were analyzed at (1) pre-treatment baseline (2) 2 weeks post-treatment and (3) as an ‘‘early change” variable defined as change in EEG from baseline to 2 weeks post-treatment.
At baseline, treatment responders showed elevated absolute alpha power in the left hemisphere while non-responders showed the opposite. Responders further exhibited a cortical asymmetry in the parietal region. Groups also differed in pre-treatment relative delta power with responders showing greater power in the right hemisphere over the left while non-responders showed the opposite. At 2 weeks post-treatment, responders exhibited greater absolute beta power in the left hemisphere relative to the right and the opposite was noted for non-responders. A reverse pattern was noted for absolute and relative delta power at 2 weeks post-treatment. Responders exhibited early reductions in relative alpha power and early increments in relative theta power. Non-responders showed a significant early increase in prefrontal theta cordance.
Hemispheric asymmetries in the alpha and delta bands at baseline and at 2 weeks post-treatment have moderately strong predictive utility in predicting response to antidepressant treatment.
•Escitalopram responders show elevated baseline alpha power in the left hemisphere.•Responders exhibit baseline cortical asymmetry in the parietal region.•Treatment responders show greater baseline delta power in the right hemisphere.•Responders and non-responders display opposite patterns of power post-treatment.•Responders exhibit early reduction in alpha power and early increment in theta power.
Identifying biological and clinical markers of treatment response in depression is an area of intense research that holds promise for increasing the efficiency and efficacy of resolving a major ...depressive episode and preventing future episodes. Collateral benefits include decreased healthcare costs and increased workplace productivity. Despite research advances in many areas, efforts to identify biomarkers have not revealed any consistently validated candidates. Studies of clinical characteristics, genetic, neuroimaging, and various biochemical markers have all shown promise in discrete studies, but these findings have not translated into a personalized medicine approach to treating individual patients in the clinic. We propose that an integrated study of a range of biomarker candidates from across different modalities is required. Furthermore, advanced mathematical modeling and pattern recognition methods are required to detect important biological signatures associated with treatment outcome. Through an informatics-based integration of the various clinical, molecular and imaging parameters that are known to be important in the pathophysiology of depression, it becomes possible to encompass the complexity of contributing factors and phenotypic presentations of depression, and identify the key signatures of treatment response.
Aim
Alterations in limbic structures may be present before the onset of serious mental illness, but whether subfield‐specific limbic brain changes parallel stages in clinical risk is unknown. To ...address this gap, we compared the hippocampus, amygdala, and thalamus subfield‐specific volumes in adolescents at various stages of risk for mental illness.
Methods
MRI scans were obtained from 182 participants (aged 12–25 years) from the Canadian Psychiatric Risk and Outcome study. The sample comprised of four groups: asymptomatic youth at risk due to family history of mental illness (Stage 0, n = 32); youth with early symptoms of distress (Stage 1a, n = 41); youth with subthreshold psychotic symptoms (Stage 1b, n = 72); and healthy comparison participants with no family history of serious mental illness (n = 37). Analyses included between‐group comparisons of brain measurements and correlational analyses that aimed to identify significant associations between neuroimaging and clinical measurements. A machine‐learning technique examined the discriminative properties of the clinical staging model.
Results
Subfield‐specific limbic volume deficits were detected at every stage of risk for mental illness. A machine‐learning classifier identified volume deficits within the body of the hippocampus, left amygdala nuclei, and medial‐lateral nuclei of the thalamus that were most informative in differentiating between risk stages.
Conclusion
Aberrant subfield‐specific changes within the limbic system may serve as biological evidence to support transdiagnostic clinical staging in mental illness. Differential patterns of volume deficits characterize those at risk for mental illness and may be indicative of a risk‐stage progression.
Finding a clinically useful neuroimaging biomarker that can predict treatment response in patients with major depressive disorder (MDD) is challenging, in part because of poor reproducibility and ...generalizability of findings across studies. Previous work has suggested that posterior hippocampal volumes in depressed patients may be associated with antidepressant treatment outcomes. The primary purpose of this investigation was to examine further whether posterior hippocampal volumes predict remission following antidepressant treatment. Magnetic resonance imaging (MRI) scans from 196 patients with MDD and 110 healthy participants were obtained as part of the first study in the Canadian Biomarker Integration Network in Depression program (CAN-BIND 1) in which patients were treated for 16 weeks with open-label medication. Hippocampal volumes were measured using both a manual segmentation protocol and FreeSurfer 6.0. Baseline hippocampal tail (Ht) volumes were significantly smaller in patients with depression compared to healthy participants. Larger baseline Ht volumes were positively associated with remission status at weeks 8 and 16. Participants who achieved early sustained remission had significantly greater Ht volumes compared to those who did not achieve remission by week 16. Ht volume is a prognostic biomarker for antidepressant treatment outcomes in patients with MDD.
Background Impairment of recollection memory is consistently reported in patients with major depressive disorder (MDD) and may reflect underlying functional hippocampal changes, particularly in those ...with extensive histories of illness. We hypothesized that relative to controls, patients with a protracted course of illness would show diminished hippocampal activation on functional magnetic resonance imaging (fMRI) during a recollection memory task. Methods Patients who experienced 3 or more previously treated depressive episodes were compared with age- and sex-matched controls. We acquired fMRI data while participants performed a recollection memory process dissociation task. Results Using bilateral regions of interest (ROIs) prescribed for the right and left hippocampal/ parahippocampal complex, we observed increased activation of the right hippocampal and left parahippocampal gyrus in controls compared with patients with MDD during recollection memory trials. Within-group comparisons revealed heightened engagement of the hippocampal head (R/L) for controls during recollection trials, and greater activation of the hippocampal body/tail (R/L) during the learn-list encoding period in both the MDD and control groups. Recollection memory performance was significantly correlated with changes in blood oxygen level–dependent signal during recollection trials in the ROIs of the right hippocampus and right hippocampal head. Limitations This study was limited by the inclusion of patients taking antidepressant medication, raising the possibility that the reported findings were treatment effects. Conclusion The findings of decreased recruitment of the right hippocampal and left parahippocampal gyrus in patients with MDD suggest that these regions may be sensitive to the impact of disease burden and repeated episodes of MDD. This attenuated activation may represent stable changes in hippocampal function that occur over the course of illness in patients with MDD. The findings from within-group comparisons show that the group differences in the activation of the right hippocampal head were driven by greater engagement of this region among controls during recollection memory performance. These results also associate recollection performance impairments in patients with MDD with diminished hippocampal engagement.
Abstract Little is known about the brain changes that mediate improvement following cognitive remediation. We used neuropsychological tests and functional magnetic resonance imaging to study working ...memory and recollection memory in patients with mood disorders, before (PRE) and after (POST) 10 weeks of cognitive remediation. Thirty-eight patients completed a recollection memory task at PRE (28 had complete PRE and POST scans) and 35 patients completed an n -back working memory task at PRE (23 had complete PRE and POST scans). We also compared patients at PRE with two groups of healthy controls subjects ( n =18 for the recollection memory task and n =15 for the working memory task). At PRE, compared to controls, patients had (i) poorer backward digit span scores, (ii) lower accuracy scores and weaker frontopolar activation during the 2-back condition, and (iii) poorer recollection scores and altered medial temporal activation on the recollection memory task. Following remediation, patients (i) improved on the backward digit span, (ii) activation increased in lateral and medial prefrontal, superior temporal, and lateral parietal regions in the 2-back condition, and (iii) recollection-related activation increased in the bilateral hippocampus. Improvements in 2-back accuracy correlated with activation increases in lateral and medial prefrontal and lateral parietal regions, and improved recollection scores correlated with activation increases in the left hippocampus. PRE–POST improvements on the backward digit span correlated with PRE–POST improvements in 2-back task accuracy; however, there was no direct association between improvement on the backward digit span following training and change in functional activation. These findings suggest that cognitive remediation may lead to behavioural improvements on tests of working memory. The relation between behavioural change and changes in functional activation following remediation requires further study.
To consider the mechanisms that may link asthma and major depressive disorder (MDD). Asthma and MDD co-occur at higher rates than expected, but whether this reflects shared underlying ...pathophysiological mechanisms is not known.
A review of the epidemiological data linking asthma and MDD was conducted and the possible biological mechanisms that could account for the high rate of this comorbidity were reviewed.
MDD occurs in almost half of patients with asthma assessed in tertiary care centers. Dysregulation of the hypothalamic pituitary adrenal axis may predispose people to both MDD and asthma, and similar alterations in the immune, autonomic nervous, and other key systems are apparent and may contribute to this increased risk of co-occurrence.
High rates of MDD in asthma may result from the stress of chronic illness, the medications used to treat it, or a combination of the two. The high level of co-occurrence may also reflect dysregulation of certain stress-sensitive biological processes that contribute to the pathophysiology of both conditions.
With improvements to both scan quality and facial recognition software, there is an increased risk of participants being identified by a 3D render of their structural neuroimaging scans, even when ...all other personal information has been removed. To prevent this, facial features should be removed before data are shared or openly released, but while there are several publicly available software algorithms to do this, there has been no comprehensive review of their accuracy within the general population. To address this, we tested multiple algorithms on 300 scans from three neuroscience research projects, funded in part by the Ontario Brain Institute, to cover a wide range of ages (3-85 years) and multiple patient cohorts. While skull stripping is more thorough at removing identifiable features, we focused mainly on defacing software, as skull stripping also removes potentially useful information, which may be required for future analyses. We tested six publicly available algorithms (afni_refacer, deepdefacer, mri_deface, mridefacer, pydeface, quickshear), with one skull stripper (FreeSurfer) included for comparison. Accuracy was measured through a pass/fail system with two criteria; one, that all facial features had been removed and two, that no brain tissue was removed in the process. A subset of defaced scans were also run through several preprocessing pipelines to ensure that none of the algorithms would alter the resulting outputs. We found that the success rates varied strongly between defacers, with afni_refacer (89%) and pydeface (83%) having the highest rates, overall. In both cases, the primary source of failure came from a single dataset that the defacer appeared to struggle with - the youngest cohort (3-20 years) for afni_refacer and the oldest (44-85 years) for pydeface, demonstrating that defacer performance not only depends on the data provided, but that this effect varies between algorithms. While there were some very minor differences between the preprocessing results for defaced and original scans, none of these were significant and were within the range of variation between using different NIfTI converters, or using raw DICOM files.
Youth at clinical high risk (CHR) for psychosis can present not only with characteristic attenuated psychotic symptoms but also may have other comorbid conditions, including anxiety and depression. ...These undifferentiated mood symptoms can overlap with the clinical presentation of youth with Distress syndromes. Increased resting-state functional connectivity within cerebello-thalamo-cortical (CTC) pathways has been proposed as a trait-specific biomarker for CHR. However, it is unclear whether this functional neural signature remains specific when compared to a different risk group: youth with Distress syndromes. The purpose of the present work was to describe CTC alterations that distinguish between CHR and Distressed individuals.
Using machine learning algorithms, we analyzed CTC connectivity features of CHR (n = 51), Distressed (n = 41), and healthy control (n = 36) participants. We found four cerebellar (lobes VII and left Crus II anterior/posterior) and two basal ganglia (right putamen and right thalamus) nodes containing a set of specific connectivity features that distinguished between CHR, Distressed and healthy control groups. Hyperconnectivity between medial lobule VIIb, somatomotor network and middle temporal gyrus was associated with CHR status and more severe symptoms. Detailed atlas parcellation suggested that CHR individuals may have dysfunction mainly within the associative (cognitive) pathways, particularly, between those brain areas responsible for the multi-sensory signal integration.
Abstract
Understanding the neural underpinnings of major depressive disorder (MDD) and its treatment could improve treatment outcomes. So far, findings are variable and large sample replications ...scarce. We aimed to replicate and extend altered functional connectivity associated with MDD and pharmacotherapy outcomes in a large, multisite sample. Resting-state fMRI data were collected from 129 patients and 99 controls through the Canadian Biomarker Integration Network in Depression. Symptoms were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). Connectivity was measured as correlations between four seeds (anterior and posterior cingulate cortex, insula and dorsolateral prefrontal cortex) and all other brain voxels. Partial least squares was used to compare connectivity prior to treatment between patients and controls, and between patients reaching remission (MADRS ≤ 10) early (within 8 weeks), late (within 16 weeks), or not at all. We replicated previous findings of altered connectivity in patients. In addition, baseline connectivity of the anterior/posterior cingulate and insula seeds differentiated patients with different treatment outcomes. The stability of these differences was established in the largest single-site subsample. Our replication and extension of altered connectivity highlighted previously reported and new differences between patients and controls, and revealed features that might predict remission prior to pharmacotherapy. Trial registration:ClinicalTrials.gov: NCT01655706.
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