Faculty Bibliography

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.

BACKGROUND AND PURPOSE/OBJECTIVE:Cerebellar heterotopia (CH) is a neuroradiologic abnormality that is poorly reported and investigated in the literature. It can be observed as an isolated finding, but it has been mainly reported in the context of cerebellar dysgenesis and syndromic conditions. This study aims to provide a comprehensive neuroradiologic, clinical, and genetic characterization of a cohort of pediatric patients with CH. MATERIALS AND METHODS/METHODS:Patients with a diagnosis of CH were systematically selected from the neuroimaging databases of the 4 Italian centers participating in this retrospective study. For each patient, information regarding demographic, clinical, genetic, and neuroradiologic data was collected. RESULTS:= 14). Isolated CH consistently showed a peripheral subcortical localization in the inferior portion of cerebellar hemispheres, with either unilateral or bilateral distribution. Ten patients belonging to the second group had a diagnosis of CHARGE syndrome, and their nodules of CH were mainly but not exclusively bilateral, symmetric, located in the peripheral subcortical zone and the inferior portion of the cerebellar hemispheres. The remaining 4 patients of the second group showed either bilateral or unilateral CH, located in both the peripheral cortex and deep white matter and the superior and inferior portions of cerebellum. Patients with isolated CH showed a high prevalence of language development delay; neurodevelopmental disorders were the most represented clinical diagnoses. Recurring features were behavioral problems and motor difficulties. A conclusive genetic diagnosis was found in 18/32 patients. CONCLUSIONS:We found distinctive neuroradiologic patterns of CH. Genetic results raise the possibility of a correlation between cerebellar morphologic and functional developmental disruption, underscoring the importance of CH detection and reporting to orient the diagnostic path.

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.

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.

IMPORTANCE/UNASSIGNED:Individuals with attention-deficit/hyperactivity disorder (ADHD) may present with psychosis or bipolar disorder (BD) following treatment with stimulants. The extent to which this occurs is currently unclear. OBJECTIVE/UNASSIGNED:To meta-analytically quantify the occurrence of psychosis or BD after exposure to stimulants in individuals with ADHD and assess possible moderating factors. DATA SOURCES/UNASSIGNED:PubMed, Web of Science, Ovid/PsycINFO, and Cochrane Central Register of Reviews were searched from inception until October 1, 2024, without language restrictions. STUDY SELECTION/UNASSIGNED:Studies of any design with DSM or International Classification of Diseases-defined ADHD populations exposed to stimulants, where psychosis or BD outcomes were evaluated. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:PRISMA Preferred Reporting Items for Systematic Reviews and Meta-analyses and MOOSE Meta-analysis of Observational Studies in Epidemiology guidelines were followed, the protocol was registered, and the Newcastle-Ottawa scale and Cochrane risk of bias-2 tool were used for quality appraisal. Random-effects meta-analysis, subgroup analyses, and meta-regressions were conducted. MAIN OUTCOMES AND MEASURES/UNASSIGNED:For the proportion of individuals developing psychotic symptoms, psychotic disorders, and BD, effect sizes are reported as percentages with 95% CIs. For the comparison between amphetamines and methylphenidate, effect sizes are presented as odds ratios with 95% CIs. RESULTS/UNASSIGNED:Sixteen studies (N = 391 043; mean [range] age, 12.6 [8.5-31.1] years; 288 199 [73.7%] male) were eligible. Among individuals with ADHD prescribed stimulants, 2.76% (95% CI, 0.73-9.88; k = 10; n = 237 035), 2.29% (95% CI, 1.52-3.40; k = 4; n = 91 437), and 3.72% (95% CI, 0.77-16.05; k = 4; n = 92 945) developed psychotic symptoms, a psychotic disorder, and BD, respectively. Heterogeneity across the studies was significant (I2 > 95%). Psychosis occurrence risk was significantly higher in individuals exposed to amphetamines than to methylphenidate (odds ratio [OR], 1.57, 95% CI, 1.15-2.16; k = 3, n = 231 325). Subgroup analyses showed significantly higher prevalence of psychotic symptoms in studies from North America and in those with longer follow-up periods. Increased psychosis occurrence was associated with a higher proportion of female participants, smaller sample sizes, and higher dose of stimulants. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This systematic review and meta-analysis found a nonnegligible occurrence of psychotic symptoms, psychotic disorders, or BD in individuals with ADHD treated with stimulants. Amphetamines were associated with higher occurrence compared to methylphenidate. The included studies cannot establish causality, highlighting the need for further research, including randomized clinical trials and mirror-image studies comparing individuals exposed and not exposed to stimulants. Nonetheless, clinicians should inform patients about the increased occurrence of psychosis or BD when discussing stimulant pharmacotherapy and systematically monitor for these conditions throughout treatment.

Chronic motor or vocal tic disorder (CMVTD) is a distressing neuropsychiatric condition. A subset of patients remains refractory to currently approved therapies. The present report describes a pediatric patient with CMVTD who had previously failed multiple pharmacological treatments, including two Food and Drug Administration (FDA)-approved agents (pimozide, aripiprazole), guanfacine, psychotherapy, and novel compounds (lumateperone, cariprazine). The patient was initiated on valbenazine, titrated to 80 mg daily. Clinical improvement was noted within 24-48 hours, with sustained benefit and good tolerability. Tic severity, measured by the Yale Global Tic Severity Scale-Revised (YGTSS-R), improved from 65 at baseline to five following treatment (net reduction of 60 points). This case illustrates a marked therapeutic response to valbenazine in a patient with CMVTD refractory to conventional and novel therapies. These observations highlight the potential role of vesicular monoamine transporter 2 (VMAT2) inhibition in tic disorders and also the need for further clinical study.

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.