ORCID Profile
0000-0002-7159-7583
Current Organisations
University of Calgary Cumming School of Medicine
,
Alberta Health Services
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Springer Science and Business Media LLC
Date: 08-12-2020
DOI: 10.1038/S41398-020-01109-5
Abstract: It has been difficult to find robust brain structural correlates of the overall severity of major depressive disorder (MDD). We hypothesized that specific symptoms may better reveal correlates and investigated this for the severity of insomnia, both a key symptom and a modifiable major risk factor of MDD. Cortical thickness, surface area and subcortical volumes were assessed from T1-weighted brain magnetic resonance imaging (MRI) scans of 1053 MDD patients (age range 13-79 years) from 15 cohorts within the ENIGMA MDD Working Group. Insomnia severity was measured by summing the insomnia items of the Hamilton Depression Rating Scale (HDRS). Symptom specificity was evaluated with correlates of overall depression severity. Disease specificity was evaluated in two independent s les comprising 2108 healthy controls, and in 260 clinical controls with bipolar disorder. Results showed that MDD patients with more severe insomnia had a smaller cortical surface area, mostly driven by the right insula, left inferior frontal gyrus pars triangularis, left frontal pole, right superior parietal cortex, right medial orbitofrontal cortex, and right supramarginal gyrus. Associations were specific for insomnia severity, and were not found for overall depression severity. Associations were also specific to MDD healthy controls and clinical controls showed differential insomnia severity association profiles. The findings indicate that MDD patients with more severe insomnia show smaller surfaces in several frontoparietal cortical areas. While explained variance remains small, symptom-specific associations could bring us closer to clues on underlying biological phenomena of MDD.
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.BIOPSYCH.2022.02.959
Abstract: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre erinatal periods may be reflected in in idual variations in cortical surface area later in life. Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 in iduals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre erinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
Publisher: American Medical Association (AMA)
Date: 2021
Publisher: Proceedings of the National Academy of Sciences
Date: 15-05-2018
Abstract: Left–right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population and how biological factors such as age, sex, and genetic variation affect these asymmetries. Here, we describe by far the largest-ever study of cerebral cortical asymmetry, based on data from 17,141 participants. We found a global anterior–posterior “torque” pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an online resource that will serve future studies of human brain anatomy in health and disease.
Publisher: Informa UK Limited
Date: 31-10-2018
DOI: 10.1080/02699052.2018.1540798
Abstract: The long-term effects of concussion in youth remain poorly understood. The objective of this study was to determine the association between history of concussion and cerebral blood flow (CBF) in youth. A total of 53 children and adolescents with a history of concussion (n = 37) or orthopaedic injury (OI n = 16) were considered. Measures included pseudo-continuous arterial spin labelling magnetic resonance imaging to quantify CBF, post-concussion symptoms, psychological symptoms, and cognitive testing. Participants (mean age: 14.4 years, 95% CI = 13.8-15.4, range = 8-19) were on average 2.7 years (95% CI = 2.2-3.1) post-injury. Youth with a history of concussion had higher parent-reported physical, cognitive, anxiety, and depression symptoms than children with OI, but the groups did not differ on self-reported symptoms (post-concussive or psychological) or cognitive testing. Global CBF did not differ between groups. Regional CBF analyses suggested that youth with a history of concussion had hypoperfusion in posterior and inferior regions and hyperperfusion in anterior/frontal/temporal regions as compared to those with OI. However, neither global nor regional CBF were significantly associated with demographics, pre-injury functioning, number of concussions, time since injury, post-concussive symptoms, psychological symptoms, or cognitive abilities. Youth with a history of concussion demonstrate differences in regional CBF (not global CBF), but without clear clinical expression.
Publisher: Springer Science and Business Media LLC
Date: 18-05-2020
DOI: 10.1038/S41380-020-0754-0
Abstract: Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 s les worldwide. Healthy brain aging was estimated by predicting chronological age (18–75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen’s d = 0.14, 95% CI: 0.08–0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.
Publisher: Springer Science and Business Media LLC
Date: 29-05-2020
DOI: 10.1038/S41398-020-0842-6
Abstract: A key objective in the field of translational psychiatry over the past few decades has been to identify the brain correlates of major depressive disorder (MDD). Identifying measurable indicators of brain processes associated with MDD could facilitate the detection of in iduals at risk, and the development of novel treatments, the monitoring of treatment effects, and predicting who might benefit most from treatments that target specific brain mechanisms. However, despite intensive neuroimaging research towards this effort, underpowered studies and a lack of reproducible findings have hindered progress. Here, we discuss the work of the ENIGMA Major Depressive Disorder (MDD) Consortium, which was established to address issues of poor replication, unreliable results, and overestimation of effect sizes in previous studies. The ENIGMA MDD Consortium currently includes data from 45 MDD study cohorts from 14 countries across six continents. The primary aim of ENIGMA MDD is to identify structural and functional brain alterations associated with MDD that can be reliably detected and replicated across cohorts worldwide. A secondary goal is to investigate how demographic, genetic, clinical, psychological, and environmental factors affect these associations. In this review, we summarize findings of the ENIGMA MDD disease working group to date and discuss future directions. We also highlight the challenges and benefits of large-scale data sharing for mental health research.
Publisher: Informa UK Limited
Date: 12-05-2020
Publisher: Springer Science and Business Media LLC
Date: 28-05-2020
DOI: 10.1038/S41380-020-0774-9
Abstract: Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI ( n = 6420) and genetic data ( n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = −0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2020
Publisher: Springer Science and Business Media LLC
Date: 30-08-2019
Publisher: American Academy of Pediatrics (AAP)
Date: 04-2020
Abstract: Approximately 25% of children with concussion have persistent postconcussive symptoms (PPCS) with resultant significant impacts on quality of life. Melatonin has significant neuroprotective properties, and promising preclinical data suggest its potential to improve outcomes after traumatic brain injury. We hypothesized that treatment with melatonin would result in a greater decrease in PPCS symptoms when compared with a placebo. We conducted a randomized, double-blind trial of 3 or 10 mg of melatonin compared with a placebo (NCT01874847). We included youth (ages 8–18 years) with PPCS at 4 to 6 weeks after mild traumatic brain injury. Those with significant medical or psychiatric histories or a previous concussion within the last 3 months were excluded. The primary outcome was change in the total youth self-reported Post-Concussion Symptom Inventory score measured after 28 days of treatment. Secondary outcomes included change in health-related quality of life, cognition, and sleep. Ninety-nine children (mean age: 13.8 years SD = 2.6 years 58% girls) were randomly assigned. Symptoms improved over time with a median Post-Concussion Symptom Inventory change score of −21 (95% confidence interval [CI]: −16 to −27). There was no significant effect of melatonin when compared with a placebo in the intention-to-treat analysis (3 mg melatonin, −2 [95% CI: −13 to 6] 10 mg melatonin, 4 [95% CI: −7 to 14]). No significant group differences in secondary outcomes were observed. Side effects were mild and similar to the placebo. Children with PPCS had significant impairment in their quality of life. Seventy-eight percent demonstrated significant recovery between 1 and 3 months postinjury. This clinical trial does not support the use of melatonin for the treatment of pediatric PPCS.
Publisher: Wiley
Date: 25-08-2020
DOI: 10.1002/HBM.25154
Abstract: The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p ‐hacking. Low statistical power in in idual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left–right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta‐analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an “ideal publishing environment,” that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% ( SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically‐used s le sizes.
Publisher: Mary Ann Liebert Inc
Date: 15-04-2021
Abstract: Sleep disturbances are commonly reported in children with persistent post-concussion symptoms (PPCS). Melatonin treatment is often recommended, yet supporting evidence is scarce. We aimed to evaluate the efficacy of treatment with melatonin for sleep disturbance in youth with PPCS following mild traumatic brain injury (mTBI). This article is a secondary analysis of a clinical trial of melatonin compared with placebo to treat PPCS. Youth (8-18 years of age) with PPCS and significant sleep-related problems (SRPs) at 4-6 weeks post-injury were eligible. Exclusion criteria: significant medical sychiatric history previous concussion/mTBI within 3 months. Treatment groups were: placebo, melatonin 3 mg, or melatonin 10 mg. Primary outcome was change in SRPs measured using the Post-Concussion Symptom Inventory (PCSI) after 2 weeks of treatment. Secondary outcomes included change in actigraphy sleep efficiency, duration, onset latency, and wake-after-sleep-onset. Behavior was measured using Behaviour Assessment for Children (2nd edition). Seventy-two participants (mean age 14.0, standard deviation [SD] = 2.6) years 60% female) with PPCS and significant sleep disturbance were included in the secondary analysis: placebo (
Publisher: American Psychiatric Association Publishing
Date: 12-2019
DOI: 10.1176/APPI.AJP.2019.18101144
Abstract: Asymmetry is a subtle but pervasive aspect of the human brain, and it may be altered in several psychiatric conditions. MRI studies have shown subtle differences of brain anatomy between people with major depressive disorder and healthy control subjects, but few studies have specifically examined brain anatomical asymmetry in relation to this disorder, and results from those studies have remained inconclusive. At the functional level, some electroencephalography studies have indicated left fronto-cortical hypoactivity and right parietal hypoactivity in depressive disorders, so aspects of lateralized anatomy may also be affected. The authors used pooled in idual-level data from data sets collected around the world to investigate differences in laterality in measures of cortical thickness, cortical surface area, and subcortical volume between in iduals with major depression and healthy control subjects. The authors investigated differences in the laterality of thickness and surface area measures of 34 cerebral cortical regions in 2,256 in iduals with major depression and 3,504 control subjects from 31 separate data sets, and they investigated volume asymmetries of eight subcortical structures in 2,540 in iduals with major depression and 4,230 control subjects from 32 data sets. T The largest effect size (Cohen's d) of major depression diagnosis was 0.085 for the thickness asymmetry of the superior temporal cortex, which was not significant after adjustment for multiple testing. Asymmetry measures were not significantly associated with medication use, acute compared with remitted status, first episode compared with recurrent status, or age at onset. Altered brain macro-anatomical asymmetry may be of little relevance to major depression etiology in most cases.
Location: United States of America
No related grants have been discovered for Frank MacMaster.