COUHR Montreal Inaugural Research Symposium Highlights

Unfolding the potential of today’s youth to discover tomorrow’s solutions

September 7, 2019
New Residence Hall
Montreal, Quebec 3625 Avenue du Parc, McGill University

Conference Abstracts

Increased Levels of Prenatal Maternal Stress are Associated with Alterations in Sexually Dimorphic Facial Regions in Children – Project Ice Storm

Xiao Xia Zhang, David P. Laplante, Suzanne King

The human face exhibits sexually dimorphic regions (cheek, chin and lower jaw). Prenatal maternal stress (PNMS) has been shown to alter fetal development, sometimes in a sex specific manner. Altered facial dimensions are often associated with behavioral disorders. The goal of this study was to see whether PNMS alters sexually dimorphic regions of children’s faces. Measurements of known facial landmarks (using digital calibers) were obtained on children exposed in utero to varying levels of disaster-related objective hardship and subjective distress when they were 5 (n = 116) and 11 (n= 87) years of age.

At age 5, increases in subjective distress correlated with smaller jaws relative to the face, particularly in girls. However, for boys, increases in objective hardship correlated with larger jaws relative to the face. Finally, increases in subjective distress correlated with increases in jaw protrusion in girls and decreases in boys. At age 11, increases in objective hardship correlated with increases in jaw height relative to the face.

Overall, objective hardship was associated with masculinization for both sexes while subjective distress was associated with masculinization in girls, but feminization in boys. It remains to be determined whether these facial alters are associated with suboptimal development.

An Accurate and Markerless Tracking of Mice Under Different Conditions Using the Deep Learning Program DeepLabCut

David Bian, Tianze Lin, Kwong Yi Kevin Lui, Donghan Liu, Amanda Larosa, Alice S. Wong, Benjamin C. M. Fung, and Tak Pan Wong Equal contribution

The behavioral tracking of a mouse is often a complicated process requiring specialized equipment that may affect the natural movement of an animal. In order to minimize the dependency on such gadgets, several markerless tracking programs have been created, including OptiMouse, an algorithm-based tracking program, and DeepLabCut, a deep learning AI. In this study, we compared the accuracy and functionality of OptiMouse and DeepLabCut. In order to test the accuracy of the two programs, the tracking analyses were compared; we examined if the predicted positions of a mouse were different to manually labeled positions, where OptiMouse was determined to have a significantly higher error rate than DeepLabCut (p<0.05). We also observed that OptiMouse sometimes did not detect every frame containing a mouse and this error occurred at a rate that was also significantly higher than DeepLabCut (p<0.05). Furthermore, while OptiMouse could only track one mouse at a time, we used DeepLabCut to accurately detect multiple mice simultaneously, with a low error rate (i.e. under 5%) that can be minimized with further refinement. Finally, we were able to demonstrate DeepLabCut’s usefulness with our current research on egocentric tuning. The behavioral tracking from DeepLabCut was used to generate data on the relative position between a social target (i.e. an enclosure) and the mouse itself. This data was used with hippocampal CA1 cell firing which was generated from a miniature fluorescent microscope to obtain useful information showing the position of the social target when the neurons fired often. Findings from this study suggest that the deep learning program DeepLabCut is a highly accurate and versatile program that can track multiple animals simultaneously which is potentially useful for studying social interaction. Additionally, we were able demonstrate an application to DeepLabCut on our current egocentric tuning project.

Systematic Review of the Utility of Physiological Measures as Trauma Treatment Outcome Measures

Michelle Yang, Outi Linnaranta

Background: Psychophysiological abnormalities have been correlated with trauma, including exaggerated startle and delayed cardiac recovery to baseline. However, the reliability of standard subjective symptom assessments can be compromised by memory biases and declarative memory dysfunction. Comparatively, dynamic emotional changes may be objectively indicated by physiological responses.

Aim: Evaluate the utility and validity of psychophysiological markers as trauma intervention outcome measures.

Methods:

Search Criteria

– A systematic review of trauma-focused interventions was conducted in PubMed, PsychInfo, and Medline databases for randomized controlled trials and longitudinal studies from inception to July 2019.

Study selection

– Twenty-one studies reporting psychophysiological measurement values at post-treatment assessment points were included.

Search Terms

– Three levels of search terms were used. This included terminology for Post-traumatic Stress Disorder, Psychophysiological measurement, and Treatment outcomes.

Review process:

– Results were grouped by theme of intervention and interpreted for trends in treatment responses

Results: Physiological measures including heart rate, heart rate variability, and skin conductance had all been used repeatedly. Changes in these correlated moderately consistently with changes in psychometrics, and using sensing technology presented the added benefit of gathering real-time data. Improving intervention content by identifying specific components of intervention demonstrated clinical utility of biomarkers, and predictive utility was seen in the markers’ sensitivity in predicting levels of treatment response from baseline measures or initial treatment sessions.

Conclusion: Psychophysiological measures are a promising objective index of PTSD treatment response that can help verify clinical impressions and self-reports. Elevated psychophysiological responses could be a pathogenic mechanism in the etiology or expression of PTSD, and thus, a means or measure of intervention. Further research is needed to confirm clinical utility of psychophysiological measures, provide valid response cut-offs, and reduce measurement error from data processing.

Nicotine Exposure In The Womb Produces Genetic And Cognitive Behavioural Changes In Offspring As Caused By Smoking Partners.

Doreen Kiprono, Barbara Barth, Patricia Silveira

Exposure to nicotine alters the trafficking and assembly of nicotinic receptors (nAChRs), leading to their up-regulation on the plasma membrane. Although the mechanism is not fully understood, nicotine-induced up-regulation is believed to contribute to nicotine addiction. The effect of cotinine, the primary metabolite of nicotine, on nAChR trafficking and assembly had not been previously extensively studied. We investigated the confounding effect a smoking partner would have on the baby and as an adult as well as the gene network related to cotinine which is used as a biomarker for nicotine exposure in the womb. A pH-sensitive variant of GFP, super ecliptic pHluorin, was used to differentiate between intracellular nAChRs and those expressed on the plasma membrane to quantify changes resulting from cotinine and nicotine exposure that were collected from the saliva of 27 tobacco-exposed and 29 unexposed full-term new born infants from comparable social backgrounds with no medical problems. The “nicotine” infants were more excitable, abnormally tense and rigid, required more handling and showed greater stress, specifically in their central nervous, gastrointestinal and visual systems. Exposure to cotinine increases the number of α4β2 receptors on the plasma membrane and causes a redistribution of intracellular receptors. Taking together the results from above, maternal active or passive smoking during pregnancy correlates with behavioural problems in the offspring across the lifespan. However, even if no study had had the possibility to investigate the longitudinal association from birth to adulthood, the results from offspring at different ages seem to support a long-lasting relationship. Central nervous system (CNS) findings Bublitz et al. reviewed the results from the small number of studies investigating the association between maternal smoking during pregnancy and brain structure and function in human offspring and concluded that this exposure has adverse effects.

Masticatory Function in Children and It’s Relationship to Macronutrients Intake During a Snack Meal Test

Doreen Kiprono, Kelly Scudine, Barbara Barth, Patricia Silveira

Description of children’s eating attitudes is important in terms of health prevention and intervention, although it has been little studied during childhood. We aimed to perform a comprehensive exploratory evaluation of behavioral aspects related to masticatory function in children. For that, 117 four years-old children and their mothers were recruited from a prospective birth cohort (Maternal Adversity, Vulnerability and Neurodevelopment – MAVAN) and evaluated during a video-recorded snack test meal. Only children’s behavior was considered for this study. Videos were coded for bites, chews and time of oral exposure using a specialized behavioral annotation software (ELAN 4.9.1) and for total amount of macronutrients intake. In relation to masticatory function, mean eating rate (calories per minute) was 31.88 (SD=15.25), average bite size was 5.36 grams (SD=3.69) and meal duration (seconds) was 1392.14 (SD=382.75). Average bite size (g) was positively and significantly correlated with total intake of calories (r=0.195; p<0.05), total intake of sugars (r=0.336; p<0.01) and total intake of protein (r=0.213; p<0.05). Eating rate (calories per minute) was positively and significantly correlated with total intake of calories (r=0.371; p<0.01), carbohydrates (r=0.242; p<0.01), sugars (r=0.277; p<0.01), protein (r=0.332; p<0.01) and fat (r=0.351; p<0.01). Meal duration was positively and significantly correlated with total intake of calories (r=0.253; p<0.01), carbohydrates (r=0.217; p<0.05), sugars (r=0.197; p<0.05), fibers (r=0.207; p<0.05) , protein (r=0.195; p<0.05) and fat (r=0.210; p<0.05). These results indicate that there is a relationship between masticatory behaviors and eating pattern in children. Higher average bite size, eating rate and meal duration seems to be related to higher intake of macronutrients, specially sugars and proteins, as well as total intake of calories per meal. Elaboration of preventions and interventions on unhealthy eating behaviors among children may benefit from these results.

The Effect of Sex on Blood Pressure Responses to Device-Guided Slow Breathing

Maha Lina Khemakhem, Charlotte Usselman

Slow breathing is a technique used to decrease blood pressure (BP) and improve cardiovascular health in various clinical populations. However, the majority of studies demonstrating the clinical effectiveness of slow breathing have been conducted in men, and it remains to be determined whether slow breathing also reduces BP in women. Given that women start with lower resting BP than men, we tested the hypothesis that slow breathing would induce smaller reductions in BP in women compared to men. Young healthy women (n=10, age: 22±2y, BMI: 22±2kg/m 2 ) and men (n=12, 23±3y, 26±4kg/m 2 ) were tested in the supine position during 15 minutes of device-guided slow breathing (RESPeRATE) while systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured on a beat-by-beat basis using finger photoplethysmography (Finometer MIDI). The mean SBP and DBP reduction for men and women combined were respectively 3.2±0.8 mmHg and 1.3±0.4 mmHg. Women had lower SBP (113 vs 121 mmHg) and DBP (68 vs 73 mmHg) compared to men at baseline. However, no interaction between sex and slow breathing was observed. In conclusion, despite the fact that men had higher SBP overall, the slow breathing-induced reduction in blood pressure was similar between sexes. Hence, these data suggest that slow breathing may be equally effective in reducing BP in hypertensive women as in men.

Misaligned Circadian Rhythm is Reflected in Irregular Rest: Activity Rhythms and Eating Patterns in Patients with a Bipolar Disorder

Elaine Tian, Clément Bourguignon, Asli Buyukkurt, Paola Lavin, Olivia Crescenzi, Outi Linnaranta

Aim: A misaligned rest:activity rhythm is a characteristic of bipolar disorders (BD). No previous studies have simultaneously evaluated sleep and eating patterns in BD.

Methods: Consenting bipolar disorder (BD) patients (n=78) were recruited from an outpatient, tertiary care clinic and fitted with wrist-actigraphy devices, which recorded their daily activity for a period of ≥10 days. During this period, they also provided subjective measurements of eating times, and patients’ mood was assessed at baseline and after two weeks. We assessed participants’ sleep patterns (center of daily inactivity [CenDI], consolidation of inactivity [ConDI]), quality of sleep (qualsleep), and eating patterns (timing [ITIM] and intervals [IINT] of food intake).

Results: Having a more irregular eating schedule was found to be correlated with more irregularity in sleep patterns (SD of CenDI with ITIM, rho = 0.48, p < 0.01, with IINT, rho = 0.42, p < 0.01, SD of onset with ITIM, rho = 0.27, p = 0.02, with IINT, rho = 0.31, p = 0.01, SD of offset with ITIM, rho = 0.30, p = 0.01, with IINT = 0.33, p < 0.01) and less consolidated sleep (SD of midpoint consolidation with ITIM, rho = -0.26, p = 0.02, with IINT, rho = -0.23, p = 0.04). Furthermore, irregularities in eating patterns were found to be correlated with more severe hypomanic symptoms in BD patients (Young Mania Rating Scale [YMRS] with ITIM, rho = 0.30, p = 0.01, with IINT, rho = 0.34, p < 0.01). In contrast, depressive symptoms were correlated with later (Montgomery-Åsberg Depression Rating Scale [MADRS] with CenDI, rho = 0.32, p = 0.01, with offset, rho = 0.33, p < 0.01) and less consolidated sleep (MADRS with ConDI, rho = -0.24, p = 0.03), as well as a lower eating frequency (MADRS with Freq, rho = -0.26, p = 0.02). A lower functionality was associated with less sleep (Social and Occupational Functionality Scale [SOFAS] with total sleep, rho = -0.41, p < 0.01) and lower quality sleep (SOFAS with ConDI, rho = 0.28, p = 0.01).

Conclusions: A misaligned rest:activity rhythm is associated with eating irregularities, and the dysregulation of both have significant associations with the mood disturbances observed in future work should confirm whether this is due to a bidirectional causal effect and/or shared dysregulation.

Measuring Anxiety in Bipolar Disorder: a Rasch analysis

Seon, Q., Hum, S., Pavlova, B., Tuineag, M., Beaulieu, S., Linnaranta, O.

Patients with bipolar disorder (BD) have an approximately 45% lifetime prevalence of anxiety disorders. Despite the associated risk of suicide, substance abuse, and worse overall outcomes, psychometric anxiety scales optimized for regular, comprehensive screening of the BD population are lacking. In this project, we sought to support a dimensional rather than categorical conceptualization of anxiety disorders. We therefore tested the suitability of combining and reducing separate questionnaires into a unidimensional scale. We evaluated the properties the Clinically Useful Anxiety Outcomes scale, Social Phobia Inventory, Panic Disorder Measurement, and Trauma Screening Questionnaire, using item response theory (IRT). 150 observations were collected from individuals diagnosed with a bipolar disorder (BDI=58; BDII= 41) at the Douglas Mental Health University Institute’s tertiary clinic at 3 time-points (an average of 22 days and 370 days after first collection). The Rasch model (IRT) identified a unidimensional construct across the 57 total items of the anxiety scales and reduced several “misbehaving” or repetitive items. Our new scale changes to the response anchors of the original scales and is optimized for brief but informative assessment. A validation study in a large, independent sample will be conducted in the near future.