Volumetric MRI Analysis of a Case of Severe Ventriculomegaly

We present a case of a 60-year-old male referred to a tertiary psychiatric facility for diagnostic assessment due to low mood and behavioral changes. Neurological examination of the patient was unremarkable. Magnetic resonance imaging (MRI) indicated overt ventriculomegaly with gross dilatation of lateral and third ventricles. Manual segmentation of gray matter, white matter and cerebrospinal fluid demonstrated that the patient had a ventricular volume almost 46 times greater than that of healthy volunteers in the same age range. Despite his striking degree of ventriculomegaly and cortical thinning, he presented primarily with psychiatric and cognitive complaints. These represented a major neurocognitive disorder. His behavior improved with a structured environment and routine instituted by the treating team. This is a dramatic example of the brain’s response to extreme structural remodeling. Elements of pluripotentiality may counteract degeneracy to preserve functions in cases of serious structural stress in the brain. Changes in the neural circuitry of emotional processing, and/or disruption in signaling pathways important for synaptogenesis may influence depression pathophysiology. How this circuitry is modified in cases of extreme structural stress such as long-standing overt ventriculomegaly, is unclear. This case demonstrates the ability of the brain to generate a normal phenotype despite structural changes that seem incompatible with advanced cognitive function, illustrating the substantial potential for adaptability and plasticity in the brain

Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder

Major depressive disorder (MDD) is a common mental disorder associated with a significant negative impact on quality of life, morbidity/mortality, and cognitive function. Individuals who suffer with MDD display lower serum/plasmatic total antioxidant potentials and reduced brain GSH levels. Also, F2-isoprostanes circulatory levels are increased in MDD subjects and are correlated with the severity of depressive symptoms. Urinary excretion of 8-OHdG seems to be higher in patients with MDD compared to healthy controls. Despite the fact that antidepressant drugs have been used for more than 50 years, their mechanism of action is still not fully understood. This paper examines preclinical (in vitro and animal model) and clinical literature on oxidative/antioxidant effects associated with antidepressant agents and discusses their potential antioxidant-related effects in the treatment of MDD. Substantial data support that MDD seems to be accompanied by elevated levels of oxidative stress and that antidepressant treatments may reduce oxidative stress. These studies suggest that augmentation of antioxidant defences may be one of the mechanisms underlying the neuroprotective effects of antidepressants in the treatment of MDD

Predicting Brain Age at Slice Level : Convolutional Neural Networks and Consequences for Interpretability

Funding Information: NE was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior— Brasil (CAPES)—Finance Code 001. MM was financed in part by the Conselho Nacional de Pesquisa—Brasil (CNPq). Funding Information: Conflict of Interest: BF had a research grant from Pfizer outside of this study.Peer reviewedPublisher PD

Prospective Assessment of Daily Patterns of Mood-Related Symptoms

Background: The Mood Rhythm Instrument (MRI) is a new self-report questionnaire that aims to assess, the presence, and timing of daily patterns of mood-related symptoms. Here, we examined the reliability of the MRI against a prospective daily investigation over the course of 15 days. As a secondary aim, we examined whether the number of items with a perceived daily pattern correlated with severity of depressive symptoms and psychological well-being.Methods: Thirty-two participants recruited from the general population were asked to prospectively fill out a daily version of the MRI (MRI-d) for 15 days. On the 16th day, they filled out the MRI, the Beck Depression Inventory (BDI) and the World Health Organization 5-item well-being index (WHO-5).Results: The MRI showed high agreement with the MRI-d, which suggests that the MRI is a valid tool to assess daily patterns of mood symptoms. The number of mood symptoms perceived as having daily peaks correlated positively with BDI scores and negatively with WHO-5 scores.Conclusions: The MRI might be a valid tool to investigate the presence of daily patterns and the timing of mood-related factors.The MRI does not seem to be influenced by recall or recency biases. Future studies should test the usefulness of this new clinical instrument in individuals with mood disorders, as well as its ability to detect changes in the daily timing of mood symptoms before and after treatment

Rhythmicity of mood symptoms in individuals at risk for psychiatric disorders

Despite emerging evidence that disruption in circadian rhythms may contribute to the pathophysiology of psychiatric disorders, there is a significant knowledge gap on the rhythmicity of psychological symptoms. Here, we aimed at investigating the rhythmicity of mood symptoms in individuals at risk for psychiatric disorders. 391 Brazilian and 317 Spanish participants completed the Self-Reporting Questionnaire-20 for non-psychotic mental disorders; the Mood Rhythm Instrument was used to assess rhythmicity of mood symptoms and the Munich ChronoType Questionnaire to assess sleep patterns. We found that the rhythmicity of specific mood-related symptoms and behaviors, particularly pessimism and motivation to exercise, were associated with being at risk for psychiatric disorders, even after controlling for sleep timing, sleep deficit, and season of data collection. We also found that the peak of some mood symptoms and behaviors were different between individuals at high vs. low risk for psychiatric disorders, with specific differences between countries. These results are consistent with previous research showing that circadian misalignment is associated with higher risk for mental health conditions. These findings also suggest that lifestyle changes preventing circadian misalignment might be useful to reduce the risk of psychiatric disorders, where cultural differences must be taken into account

Validation of the English version of the Mood Rhythm Instrument

Background: Disruption of biological rhythms has been linked to the pathophysiology of mental disorders. However, little is known regarding the rhythmicity of mood symptoms due to the lack of validated clinical questionnaires. A better understanding of the rhythmicity of mood symptoms can help identifying individuals whose severity of mood symptoms follows an altered circadian rhythm. The objective of this study was to validate the English version of the Mood Rhythm Instrument (MRhI), a self-reported measure of self-perceived rhythmicity of mood symptoms and behaviours, in a sample of the general population from Canada. Methods: After the translation process, the final English version of the Mood Rhythm Instrument (MRhI-English) was applied on participants recruited at McMaster University and St. Joseph's Healthcare Hamilton campuses. Individuals were also asked to answer the Reduced Morningness-Eveningness Questionnaire (rMEQ). Results: Four hundred one individuals completed the English version of the MRhI and the rMEQ. The MRhI-English presented a Cronbach's alpha of 0.75. The factorial analysis grouped the MRhI-15 items in 3 factors (cognitive, affective and somatic), with affective items having a lower frequency of self-reported 24-h peaks. Comparison between sexes showed that women reported a higher frequency of daily peaks in irritability, anxiety, sadness and talking to friends, while men exhibited peaks more frequently in problem-solving, sexual arousal and motivation to exercise. Conclusions: Our findings suggest that the English version of the MRhI displayed good internal consistency. Future directions will include the use of the MRhI instrument in individuals with mood disorders, aiming to provide a better understanding of the relationship between daily patterns of mood variability and mental health outcomes

Standardization of electroencephalography for multi-site, multi-platform and multi-investigator studies: Insights from the canadian biomarker integration network in depression

Subsequent to global initiatives in mapping the human brain and investigations of neurobiological markers for brain disorders, the number of multi-site studies involving the collection and sharing of large volumes of brain data, including electroencephalography (EEG), has been increasing. Among the complexities of conducting multi-site studies and increasing the shelf life of biological data beyond the original study are timely standardization and documentation of relevant study parameters. We presentthe insights gained and guidelines established within the EEG working group of the Canadian Biomarker Integration Network in Depression (CAN-BIND). CAN-BIND is a multi-site, multi-investigator, and multiproject network supported by the Ontario Brain Institute with access to Brain-CODE, an informatics platform that hosts a multitude of biological data across a growing list of brain pathologies. We describe our approaches and insights on documenting and standardizing parameters across the study design, data collection, monitoring, analysis, integration, knowledge-translation, and data archiving phases of CAN-BIND projects. We introduce a custom-built EEG toolbox to track data preprocessing with open-access for the scientific community. We also evaluate the impact of variation in equipment setup on the accuracy of acquired data. Collectively, this work is intended to inspire establishing comprehensive and standardized guidelines for multi-site studies

Rasch analyses of the Quick Inventory of Depressive Symptomatology Self-Report in neurodegenerative and major depressive disorders

BackgroundSymptoms of depression are present in neurodegenerative disorders (ND). It is important that depression-related symptoms be adequately screened and monitored in persons living with ND. The Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) is a widely-used self-report measure to assess and monitor depressive severity across different patient populations. However, the measurement properties of the QIDS-SR have not been assessed in ND.AimTo use Rasch Measurement Theory to assess the measurement properties of the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) in ND and in comparison to major depressive disorder (MDD).MethodsDe-identified data from the Ontario Neurodegenerative Disease Research Initiative (NCT04104373) and Canadian Biomarker Integration Network in Depression (NCT01655706) were used in the analyses. Five hundred and twenty participants with ND (Alzheimer’s disease or mild cognitive impairment, amyotrophic lateral sclerosis, cerebrovascular disease, frontotemporal dementia and Parkinson’s disease) and 117 participants with major depressive disorder (MDD) were administered the QIDS-SR. Rasch Measurement Theory was used to assess measurement properties of the QIDS-SR, including unidimensionality and item-level fit, category ordering, item targeting, person separation index and reliability and differential item functioning.ResultsThe QIDS-SR fit well to the Rasch model in ND and MDD, including unidimensionality, satisfactory category ordering and goodness-of-fit. Item-person measures (Wright maps) showed gaps in item difficulties, suggesting poor precision for persons falling between those severity levels. Differences between mean person and item measures in the ND cohort logits suggest that QIDS-SR items target more severe depression than experienced by the ND cohort. Some items showed differential item functioning between cohorts.ConclusionThe present study supports the use of the QIDS-SR in MDD and suggest that the QIDS-SR can be also used to screen for depressive symptoms in persons with ND. However, gaps in item targeting were noted that suggests that the QIDS-SR cannot differentiate participants falling within certain severity levels. Future studies would benefit from examination in a more severely depressed ND cohort, including those with diagnosed clinical depression