Faculty Bibliography

BACKGROUND:The precise etiology of septo-optic dysplasia (SOD) remains elusive, to date a complex interaction between genetic predisposition and prenatal exposure to environmental factors is believed to come into play. Being SOD such a heterogeneous condition, disruption of many developmental steps in the early forebrain development might occur. The knowledge of genes possibly determining SOD phenotype should be improved, therefore in this review the authors attempt to highlight the genetic pathways and genes related to this clinical condition. MAIN BODY/METHODS:Literature search was conducted and updated in November 2023, using PubMed and Google Scholar to identify primary research articles or case reports with available full text using the following search string "case reports," "humans," "septo-optic dysplasia," "optic nerve hypoplasia," with a recognized genetic diagnosis. Moreover, a review of genetic pathways with an involvement in SOD etiology was conducted. This review thus represents the authors' perspective based on selected literature. The several pathways presented might be already associated to other disease phenotypes and interplay with genes and pathways known to have a role in SOD determination. Those pathways may converge and thus, the implicated genes may function as cascading regulators at multiple levels. CONCLUSION/CONCLUSIONS:The present data suggest that genes other than HESX1, SOX2, SOX3, and OTX2 might be investigated in candidate individuals with a clinical diagnosis of SOD corresponding to the presence of at least two diagnostic criteria, particularly in the presence of additional syndromic anomalies.

BACKGROUND/UNASSIGNED:The Yazidi people are a Kurdish religious minority group who have been persecuted by the Islamic State of Iraq and Syria (ISIS). The complexity of the trauma the Yazidi people endured, and a limited understanding of their illness belief models have created challenges to providing culturally sensitive psychiatric care. The purpose of this study was to use focus group methodology to understand Yazidi refugees' experiences, to provide culturally informed mental health care. METHODS/UNASSIGNED:Two in-person focus groups were held in Calgary, Alberta with Yazidi refugee women from Iraq and Syria (N = 6, N = 7) to assess perspectives on mental health, preferred coping strategies and perceived barriers to care. Participants were selected using purposive sampling. Focus group design and facilitation were done in partnership with Yazidi cultural brokers and interpreters. Focus groups were conducted in English and interpreted in Kurmanji. The focus groups were recorded, coded, and subjected to qualitative content thematic analyses. The analysis was guided by an interpretivist epistemology and informed by pragmatism, to situate participants' perspectives within their social context while generating culturally informed insights for psychiatric care in Canada. RESULTS/UNASSIGNED:Experiences with psychiatric symptoms (e.g. grief and loss, somatization, depression, trauma) were identified. Family reunification and community support were emphasized as preferred coping methods. Perceived unrealistic expectations of refugees post-migration, social isolation and language difficulties were acknowledged as barriers to care. CONCLUSION/UNASSIGNED:Providing appropriate psychiatric care to Yazidi refugee women requires a culturally informed approach. Findings in this study support the need for culturally sensitive mental health interventions in refugee populations post migration.

Cerebellar dysfunction affects socio-affective abilities beyond motor control. Recent studies suggest that non-invasive cerebellar neurostimulation can modulate social cognition networks, offering potential therapeutic benefits for children with autism, ADHD, and mood disorders. However, its application in pediatrics remains largely unexplored. This review summarizes emerging pediatric research on cerebellar transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). We discuss their mechanisms, potential benefits, and safety considerations, highlighting preliminary findings that suggest feasibility and effectiveness. Ethical concerns and technical challenges related to pediatric neuroanatomy and stimulation parameters are also addressed. While early results are promising, further clinical trials and neurophysiological studies are essential to optimize protocols and confirm long-term efficacy. Advancing our understanding of cerebellar involvement in socio-affective functions could lead to innovative rehabilitation strategies for neurodevelopmental disorders.

Parental depression is a risk factor for children's cognitive and psychological development. Literature has found reciprocal relations between parental depression and child psychopathology and effects of parental depression on children's cognition. The present study is the first to examine reciprocity among parental depression and child cognition, and pathways to child psychopathology. Structural equation models were conducted using data from the Early Head Start Research and Evaluation Project, a nationally representative sample of 3,001 economically marginalized families. Measures were collected in four waves from 14 months to 10-11 years. Reciprocal associations emerged between maternal and paternal depression at from 14 months to 5 years. Reciprocal parental depression was associated with greater psychopathology at age 10-11. Maternal depression predicted poorer child cognition, which indirectly predicted increased depression in mothers of children aged 3-5 through paternal depression, and in fathers at age 3, through earlier paternal depression. This study was unable to parse within- and between-person effects. Additionally, data for paternal depression was limited to ages 2 and 3. Findings emphasize the transactional nature of child cognition and child and parent psychopathology, supporting family focused intervention and prevention efforts that target parent psychopathology and child cognition.

The rapid development and clinical use of brain stimulation has renewed debates about whether to define and accredit a pathway for clinical subspecialty training. To address this, the Brain Stimulation Subspecialty Summits (BraSSS) were convened in 2023 and 2024, featuring international leaders in brain stimulation across psychiatry, neurology, neurosurgery, psychology, and neuroscience. Both meetings included two days of lectures and debates focused on clinical content, emerging science, and educational standards. The 2023 meeting was held at Brigham & Women's Hospital and Harvard University, where 54 attendees reached a consensus that the subspecialty is adequately developed to warrant formal recognition and initiated debates regarding the name and scope of the subspecialty. The 2024 meeting was held at Stanford University, where 56 attendees developed a content outline, organized committees, and reached a consensus to form an independent society focused on developing and maintaining unbiased accreditation standards. "Brain stimulation" was chosen democratically as the name of the subspecialty. Clinicians from multiple primary specialties may enter this subspecialty training track. While individual programs may have a specific area of focus (e.g. interventional psychiatry or epilepsy), our expectation is that accredited brain stimulation programs will provide training experiences that cross specialties and stimulation modalities. Several potential unintended consequences were discussed, and plans were developed to address them. Overall, subspecialty recognition was deemed to be beneficial to the brain stimulation field, with a goal to launch an associated society and start the process of accrediting existing US and Canadian programs in 2025.

Serotonergic psychedelics and 3,4-methylendioxtmethamphetamine (MDMA) are promising treatments for mental disorders with a continuously evolving evidence base. We searched Pubmed/Scopus/clinical trial registries up to 08july2025 for double-blind randomized controlled trials (RCTs) testing MDMA or serotonergic psychedelics in patients with mental disorders. Primary outcomes were change in disease-specific symptoms and all-cause discontinuation. Standardized mean differences (SMD) and relative risk (RR) were estimated using random-effects meta-analysis. Risk of bias (RoB) was assessed with Cochrane's RoB-tool version 2 and certainty of evidence with GRADE. The review is maintained as living systematic review (https://ebipsyche-database.org/). We included 30 RCTs (1480 participants; female=45.8 %; with psychological support=83.3 %; high RoB=83.3 %). In post-traumatic stress disorder (PTSD), MDMA reduced PTSD symptoms compared to any control (k = 11; SMD=-0.85 [-1.09; -0.60]; I²=0 %; GRADE=low). In major depressive disorder (MDD), psilocybin/ayahuasca/LSD reduced depressive symptoms (k = 8; SMD=-0.62 [-0.97; -0.28]; I²=55 %; GRADE=very low). In anxiety disorders, both MDMA and serotonergic psychedelics reduced anxiety symptoms (SMD_MDMA=-1.18 [-2.04; -0.32]; I²=0 %; k = 2; GRADE=low and SMD_serotonergic=-0.88 [-1.70; -0.06]; I²=54 %;k = 5; GRADE=very low). In alcohol use disorder, neither psilocybin nor LSD reduced abstinence rates (k = 6; RR=1.42 [0.89; 2.26]; I²=7 %; GRADE=very low). In attention-deficit hyperactivity disorder (ADHD), LSD did not reduce ADHD symptoms (k = 1; SMD=0.22 [-0.32; 0.76]; GRADE=very low). Moderate certainty in evidence was only found for MDMA on PTSD symptoms when compared to placebo. MDMA/serotonergic psychedelics were not associated with higher risk of all-cause discontinuation (RR_MDMA=0.74 [0.32; 1.72]; RR_serotonergic=0.81 [0.56; 1.15]). Overall, MDMA/serotonergic psychedelics are promising for the treatment of PTSD, MDD, and anxiety disorders with moderate to large effect sizes. Pragmatic trials, long-term, head-to-head trials exploring the role of psychological support, aiming to identify predictors of response, and accounting for expectancy and functional unblinding are needed. Studies addressing these limitations will likely be required for regulatory approval of psychedelic drugs.

INTRODUCTION/UNASSIGNED:Comorbidity between disorders is pervasive, and its relationship to the main conditions under investigation needs to be addressed for robust causal inference. However, many clinical etiologic studies still fail to capitalize on the theoretical advancements and improved recommendations regarding covariate adjustment in this context. Specifically, studies often lack explicit causal assumptions about the role of comorbidity in exposure-outcome relationships, potentially leading to inappropriate accounting for comorbid conditions and resulting in biased effect estimates. This study aims to explore common causal structures involving comorbidity and provide guidance for handling it in etiologic research. METHODS/UNASSIGNED:We use Directed Acyclic Graphs (DAGs) to depict six causal scenarios involving comorbidity as a confounder, mediator, collider, or consequence of the exposure or outcome, illustrated with real-world clinical examples. Simulations were conducted across 5,000 iterations for each scenario, assessing the impact of conditioning on comorbidity under four effect measures (risk difference, odds ratio, risk ratio, and mean difference). Bias was evaluated by comparing adjusted and unadjusted effect estimates to the true values. RESULTS/UNASSIGNED:The impact of conditioning on comorbidity varied by its causal role. Adjusting for comorbidity mitigated bias when it acted as a confounder but introduced bias when it was a mediator or collider. In instances where comorbidity was a consequence of either the exposure or outcome, the decision to adjust depended on the research objectives and could vary across effect measures. DISCUSSION/UNASSIGNED:Explicit causal assumptions are essential for selecting appropriate analytical strategies in etiologic research. This study provides practical guidance on analytical handling of the measures of comorbidity, highlighting the need for study design and analysis to align with research objectives. Future work should address more complex causal structures and other methodological challenges.

Advanced EEG technology has revealed that epileptiform activity occurs more frequently in Alzheimer's disease (AD) than previously recognized, prompting debate over the utility of EEG in AD diagnostics. Yet, unlike epilepsy, epileptiform activity is not always observed in AD, leading to skepticism. Historically, this absence has been attributed to limited recording depth or insufficient recording duration. We tested an alternative hypothesis that certain types of epileptiform activity, specifically high-frequency oscillations (HFOs, defined as 250-500Hz fast ripples), inhibit interictal spikes (IIS), which are currently used to assess hyperexcitability clinically. We recorded wideband (0.1-500Hz) hippocampal local field potentials in three AD (Tg2576, Presenilin 2^-/-, Ts65Dn Down syndrome model) and two epilepsy (intrahippocampal kainic acid, pilocarpine) mouse models during wakefulness and sleep. In both AD and epilepsy, HFOs consistently outnumbered IIS across behavioral states, age and recording contact. However, IIS and HFOs showed divergent relationships: a negative correlation between their rates was observed only in AD, in contrast to a positive correlation in epilepsy. HFOs preceded IIS at much shorter intervals in epilepsy than in AD. Co-occurrence of IIS with ripples did not differ between AD and epilepsy. These findings reveal a novel dissociation between clinically-relevant EEG biomarkers in AD and epilepsy. In AD, HFOs may inhibit IIS, which could lead to underestimation of hyperexcitability and hinder patient stratification for anti-seizure therapies. While non-invasive HFO detection remains challenging, we stress the need for wideband EEG/MEG, particularly in AD, to assess the full extent of hyperexcitability and biomarker interactions that would otherwise remain undetected.

Interoceptive accuracy, the ability to correctly perceive internal body signals such as heartbeats, has been empirically and theoretically linked to stress. However, issues with the measurement of both interoceptive accuracy and stress have led to lack of clarity regarding this relationship. This systematic review and meta-analysis aimed to clarify whether interoceptive accuracy is associated with different facets of stress, including - physical, cognitive and self-reported stressors and the physiological stress response. A systematic search identified 2014 abstracts. Twenty-eight authors were contacted to request data for eligible studies, which yielded a final sample of 20 studies. Results revealed a positive association between heartbeat counting task (HCT) performance and acute physical stressors, and a negative association between HCT performance and physiological stress responses. No significant relationships were observed between stress and interoceptive accuracy assessed by the heartbeat discrimination task. While these findings offer tentative support for stress-interoceptive accuracy associations, they must be interpreted with caution given substantial heterogeneity in stress measures, limited use of interoception tasks beyond the HCT, and ongoing concerns regarding task validity. Implications for future research and methodological recommendations are discussed.