Long-term safety and efficacy of focused ultrasound capsulotomy for obsessive-compulsive disorder and major depressive disorder.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) trials targeting the anterior limb of the internal capsule have shown promising results. We evaluate the long-term safety and efficacy of MRgFUS capsulotomy in patients with obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). METHODS: This phase I single center open label study recruited treatment-resistant OCD and MDD. Outcomes were measured 6mo, 12mo, and 18-24months (long-term) after MRgFUS capsulotomy. Neuropsychological testing and neuroimaging were conducted at baseline and 12mo postoperatively. The primary outcome was safety. The secondary outcome was clinical response, defined for OCD as ≥35% improvement in Yale-Brown obsessive-compulsive scale (YBOCS) scores, and for MDD as a ≥50% reduction in the Hamilton Depression Rating Scale (HAMD-17) scores, compared to baseline. RESULTS: No serious adverse effects were registered. In patients with OCD (n=15), baseline YBOCS scores (31.9±1.2) were significantly reduced by 23% (p=0.01) at 6mo and 35% (p<0.0001) at 12mo. In patients with MDD (n=12), a 26% and 25% non-significant reduction in HAMD-17 scores (baseline 24.3±1.2) was observed at 6mo and 12mo, respectively. Neuropsychological testing revealed no negative effects of capsulotomy. In the OCD and MDD cohorts we found a correlation between clinical outcome and lesion laterality, with more medial left (OCD, p=0.08) and more lateral right (MDD, p<0.05) placed lesions being respectively associated with a stronger response. In the MDD cohort, more ventral tracts appeared to be associated with a poorer response. CONCLUSIONS: MRgFUS capsulotomy is safe in patients with OCD and MDD and particularly effective in the former population.

A systematic review of structural and functional magnetic resonance imaging studies on the neurobiology of depressive symptoms in schizophrenia spectrum disorders.

Depressive symptoms in Schizophrenia Spectrum Disorders (SSDs) negatively impact suicidality, prognosis, and quality of life. Despite this, efficacious treatments are limited, largely because the neural mechanisms underlying depressive symptoms in SSDs remain poorly understood. We conducted a systematic review to provide an overview of studies that investigated the neural correlates of depressive symptoms in SSDs using neuroimaging techniques. We searched MEDLINE, PsycINFO, EMBASE, Web of Science, and Cochrane Library databases from inception through June 19, 2023. Specifically, we focused on structural and functional magnetic resonance imaging (MRI), encompassing: (1) T1-weighted imaging measuring brain morphology; (2) diffusion-weighted imaging assessing white matter integrity; or (3) T2*-weighted imaging measures of brain function. Our search yielded 33 articles; 14 structural MRI studies, 18 functional (f)MRI studies, and 1 multimodal fMRI/MRI study. Reviewed studies indicate potential commonalities in the neurobiology of depressive symptoms between SSDs and major depressive disorders, particularly in subcortical and frontal brain regions, though confidence in this interpretation is limited. The review underscores a notable knowledge gap in our understanding of the neurobiology of depression in SSDs, marked by inconsistent approaches and few studies examining imaging metrics of depressive symptoms. Inconsistencies across studies' findings emphasize the necessity for more direct and comprehensive research focusing on the neurobiology of depression in SSDs. Future studies should go beyond "total score" depression metrics and adopt more nuanced assessment approaches considering distinct subdomains. This could reveal unique neurobiological profiles and inform investigations of targeted treatments for depression in SSDs.

Heterogeneity of Cognition in Older Adults with Remitted Major Depressive Disorder: A Latent Profile Analysis.

OBJECTIVES: To identify data-driven cognitive profiles in older adults with remitted major depressive disorder (rMDD) with or without mild cognitive impairment (MCI) and examine how the profiles differ regarding demographic, clinical, and neuroimaging measures. DESIGN: Secondary cross-sectional analysis using latent profile analysis. SETTING: Multisite clinical trial in Toronto, Canada. PARTICIPANTS: One hundred seventy-eight participants who met DSM-5 criteria for rMDD without MCI (rMDD-MCI; n = 60) or with MCI (rMDD + MCI; n = 118). MEASUREMENTS: Demographic, clinical, neuroimaging measures, and domain scores from a neuropsychological battery assessing verbal memory, visuospatial memory, processing speed, working memory, language, and executive function. RESULTS: We identified three latent profiles: Profile 1 (poor cognition; n = 75, 42.1%), Profile 2 (intermediate cognition; n = 75, 42.1%), and Profile 3 (normal cognition; n = 28, 15.7%). Compared to participants with Profile 3, those with Profile 1 or 2 were older, had lower education, experienced a greater burden of medical comorbidities, and were more likely to have MCI. The profiles did not differ on the severity of residual symptoms, age of onset of rMDD, number of depressive episodes, psychotropic medication, cerebrovascular risk, ApoE4 carrier status, or family history of depression, dementia, or Alzheimer's disease. The profiles differed in cortical thickness of 15 regions, with the most prominent effects for left precentral and pars opercularis, and right inferior parietal and supramarginal. CONCLUSION: Older patients with rMDD can be grouped cross-sectionally based on data-driven cognitive profiles that differ from the absence or presence of a diagnosis of MCI. Future research should determine the differential risk for dementia of these data-driven subgroups.

Virtual Reality for Developing Patient-Facing Communication Skills in Medical and Graduate Education: Protocol for a Scoping Review.

BACKGROUND: Clinician-patient communication is an integral component in providing quality medical care. However, research on clinician-patient communication has shown overall patient discontent with provider communication skills. While virtual reality (VR) is readily used for procedural-based learning in medical education, its potential for teaching patient-facing communication skills remains unexplored. This scoping review aims to evaluate the effectiveness and feasibility of VR applications used for patient-facing communication skills development in medical education. OBJECTIVE: The primary objective is to synthesize and evaluate the effectiveness of available VR tools and applications used for patient-facing communication skills development in medical education. The secondary objectives are to (1) assess the feasibility of adapting VR applications to develop patient-facing communication skills in medical education and (2) provide an overview of the challenges associated with adapting VR applications to develop patient-facing communication skills in medical education. METHODS: A total of 4 electronic databases (ERIC, Embase, PubMed, and MEDLINE) were searched for primary peer-reviewed articles published through April 11, 2023. Articles evaluating the implementation of non-, semi-, and fully immersive VR training for patient- or caregiver-facing communication skills training provided to graduate, medical, or other allied health care professions students were included. Studies that assessed augmented reality, mixed reality, artificial intelligence, or VR for non-communication-based training were excluded. Study selection will include a title, abstract, and full-text screening by 4 authors. Data from eligible studies will be extracted and entered into a database and presented in tabular format. Findings will be reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for scoping reviews. RESULTS: As of April 11, 2023, the search strategy has been confirmed and the search has been completed. We are currently at the title and abstract screening stage. Once complete, the articles will undergo full-text screening according to eligibility criteria as described in the methods. CONCLUSIONS: The findings of this review will inform the development of a graduate-level clinical skills research course within the Institute of Medical Science graduate department at the University of Toronto. It is also expected that these findings will be of interest to other health care-specific faculties inside and beyond our institution. Further, our scoping review will summarize the limited field of literature on VR use in medical communications training and identify areas for future inquiry. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53901.

Cognitive Outcomes After Antidepressant Pharmacotherapy for Late-Life Depression: A Systematic Review and Meta-Analysis.

OBJECTIVE: The authors evaluated whether treatment of late-life depression (LLD) with antidepressants leads to changes in cognitive function. METHODS: A systematic review and meta-analysis of prospective studies of antidepressant pharmacotherapy for adults age 50 or older (or mean age of 65 or older) with LLD was conducted. MEDLINE, EMBASE, and PsycInfo were searched through December 31, 2022. The primary outcome was a change on cognitive test scores from baseline to after treatment. Secondary outcomes included the effects of specific medications and the associations between changes in depressive symptoms and cognitive test scores. Participants with bipolar disorder, psychotic depression, dementia, or neurological disease were excluded. Findings from all eligible studies were synthesized at a descriptive level, and a random-effects model was used to pool the results for meta-analysis. RESULTS: Twenty-two studies were included. Thirteen of 19 studies showed an improvement on at least one cognitive test after antidepressant pharmacotherapy, with the most robust evidence for the memory and learning (nine of 16 studies) and processing speed (seven of 10 studies) domains and for sertraline (all five studies). Improvements in depressive symptoms were associated with improvement in cognitive test scores in six of seven relevant studies. The meta-analysis (eight studies; N=493) revealed a statistically significant overall improvement in memory and learning (five studies: effect size=0.254, 95% CI=0.103-0.404, SE=0.077); no statistically significant changes were seen in other cognitive domains. The evaluated risk of publication bias was low. CONCLUSION: Antidepressant pharmacotherapy of LLD appears to improve certain domains of cognitive function, particularly memory and learning. This effect may be mediated by an improvement in depressive symptoms. Studies comparing individuals receiving pharmacotherapy with untreated control participants are needed.

A simple semi-automated home-tank method and procedure to explore classical associative learning in adult zebrafish.

The zebrafish is a laboratory species that gained increasing popularity the last decade in a variety of subfields of biology, including toxicology, ecology, medicine, and the neurosciences. An important phenotype often measured in these fields is behaviour. Consequently, numerous new behavioural apparati and paradigms have been developed for the zebrafish, including methods for the analysis of learning and memory in adult zebrafish. Perhaps the biggest obstacle in these methods is that zebrafish is particularly sensitive to human handling. To overcome this confound, automated learning paradigms have been developed with varying success. In this manuscript, we present a semi-automated home tank-based learning/memory test paradigm utilizing visual cues, and show that it is capable of quantifying classical associative learning performance in zebrafish. We demonstrate that in this task, zebrafish successfully acquire the association between coloured-light and food reward. The hardware and software components of the task are easy and cheap to obtain and simple to assemble and set up. The procedures of the paradigm allow the test fish to remain completely undisturbed by the experimenter for several days in their home (test) tank, eliminating human handling or human interference induced stress. We demonstrate that the development of cheap and simple automated home-tank-based learning paradigms for the zebrafish is feasible. We argue that such tasks will allow us to better characterize numerous cognitive and mnemonic features of the zebrafish, including elemental as well as configural learning and memory, which will, in turn, also enhance our ability to study neurobiological mechanisms underlying learning and memory using this model organism.

Brain-cognition relationships in late-life depression: a systematic review of structural magnetic resonance imaging studies.

BACKGROUND: Most patients with late-life depression (LLD) have cognitive impairment, and at least one-third meet diagnostic criteria for mild cognitive impairment (MCI), a prodrome to Alzheimer's dementia (AD) and other neurodegenerative diseases. However, the mechanisms linking LLD and MCI, and brain alterations underlying impaired cognition in LLD and LLD + MCI remain poorly understood. METHODS: To address this knowledge gap, we conducted a systematic review of studies of brain-cognition relationships in LLD or LLD + MCI to identify circuits underlying impaired cognition in LLD or LLD + MCI. We searched MEDLINE, PsycINFO, EMBASE, and Web of Science databases from inception through February 13, 2023. We included studies that assessed cognition in patients with LLD or LLD + MCI and acquired: (1) T1-weighted imaging (T1) measuring gray matter volumes or thickness; or (2) diffusion-weighted imaging (DWI) assessing white matter integrity. Due to the heterogeneity in studies, we only conducted a descriptive synthesis. RESULTS: Our search identified 51 articles, resulting in 33 T1 studies, 17 DWI studies, and 1 study analyzing both T1 and DWI. Despite limitations, reviewed studies suggest that lower thickness or volume in the frontal and temporal regions and widespread lower white matter integrity are associated with impaired cognition in LLD. Lower white matter integrity in the posterior cingulate region (precuneus and corpus callosum sub-regions) was more associated with impairment executive function and processing speed than with memory. CONCLUSION: Future studies should analyze larger samples of participants with various degrees of cognitive impairment and go beyond univariate statistical models to assess reliable brain-cognition relationships in LLD.

Brain-Cognition Associations in Older Patients With Remitted Major Depressive Disorder or Mild Cognitive Impairment: A Multivariate Analysis of Gray and White Matter Integrity.

BACKGROUND: Almost half of older patients with major depressive disorder (MDD) present with cognitive impairment, and one-third meet diagnostic criteria for mild cognitive impairment (MCI). However, mechanisms linking MDD and MCI remain unclear. We investigated multivariate associations between brain structural alterations and cognition in 3 groups of older patients at risk for dementia, remitted MDD (rMDD), MCI, and rMDD+MCI, as well as cognitively healthy nondepressed control participants. METHODS: We analyzed magnetic resonance imaging data and cognitive domain scores in participants from the PACt-MD (Prevention of Alzheimer's Disease With Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression) study. Following quality control, we measured cortical thickness and subcortical volumes of selected regions from 283 T1-weighted scans and fractional anisotropy of white matter tracts from 226 diffusion-weighted scans. We assessed brain-cognition associations using partial least squares regressions in the whole sample and in each subgroup. RESULTS: In the entire sample, atrophy in the medial temporal lobe and subregions of the motor and prefrontal cortex was associated with deficits in verbal and visuospatial memory, language skills, and, to a lesser extent, processing speed (p < .0001; multivariate r = 0.30, 0.34, 0.26, and 0.18, respectively). Widespread reduced white matter integrity was associated with deficits in executive functioning, working memory, and processing speed (p = .008; multivariate r = 0.21, 0.26, 0.35, respectively). Overall, associations remained significant in the MCI and rMDD+MCI groups, but not the rMDD or healthy control groups. CONCLUSIONS: We confirm findings of brain-cognition associations previously reported in MCI and extend them to rMDD+MCI, but similar associations in rMDD are not supported. Early-onset and treated MDD might not contribute to structural alterations associated with cognitive impairment.

Age-dependent effects of embryonic ethanol exposure on anxiety-like behaviours in young zebrafish: A genotype comparison study.

Fetal Alcohol Spectrum Disorder (FASD) is characterized by a variety of morphological, behavioural and cognitive deficits, ranging from mild to severe. Numerous animal models, including the zebrafish, have been employed to better understand the onset, expression and progression of this disorder. Embryonic ethanol-induced deficits in learning and memory, anxiety, social responses and elevated alcohol self-administration have been successfully demonstrated in zebrafish. Studies in zebrafish have also shown the expression of these behavioural deficits depends upon the developmental stage of ethanol exposure, the age of observation, as well as the genotype (strain or population origin) of the tested zebrafish. Here, we investigate how the genotype and age of observation may influence embryonic ethanol-induced alterations in anxiety-like responses in zebrafish. Zebrafish embryos exposed to either 0% or 1% (vol/vol) ethanol at 24hpf were tested in an open tank at one of three stages: larval (6-8 days post fertilization (dpf)), mid-larval (16-18dpf), or juvenile (26-28dpf). Two genotypes were tested in this manner, ABNS (a quasi-inbred strain) and ABSK (a mix of AB, TU and TL strains). We found embryonic ethanol induced behavioural changes to significantly differ depending on the genotype and age of observation. For example, significant differences between control and ethanol exposed zebrafish in both genotypes were observed in juvenile zebrafish, but few significant treatment effects were observed in larval zebrafish. Additionally, ethanol appeared to alter anxiety-like behaviours in the ABNS genotype but did not have as robust of an effect on the ABSK genotype. Lastly, there were significant behavioural differences between unexposed (control) zebrafish of the two genotypes, suggesting baseline behavioural differences despite a common AB genetic origin.