Intracortical Myelin in Youths at Risk for Depression.

Background: Major depressive disorder (MDD) is a leading cause of disability. To understand why depression develops, it is important to distinguish between early neural markers of vulnerability that precede the onset of MDD and features that develop during depression. Recent neuroimaging findings suggest that reduced global and regional intracortical myelination (ICM), especially in the lateral prefrontal cortex, may be associated with depression, but it is unknown whether it is a precursor or a consequence of MDD. The study of offspring of affected parents offers the opportunity to distinguish between precursors and consequences by examining individuals who carry high risk at a time when they have not experienced depression. Methods: We acquired 129 T1-weighted and T2-weighted scans from 56 (25 female) unaffected offspring of parents with depression and 114 scans from 63 (34 female) unaffected offspring of parents without a history of depression (ages 9 to 16 years). To assess scan quality, we calculated test-retest reliability. We used the scan ratios to calculate myelin maps for 68 cortical regions. We analyzed data using mixed-effects modeling. Results: ICM did not differ between high and low familial risk youths in global (B = 0.06, SE = 0.03, p = .06) or regional (B = 0.05, SE = 0.03, p = .08) analyses. Our pediatric sample had high ICM reliability (intraclass correlation coefficient = 0.79; 95% CI, 0.55-0.88). Conclusions: Based on our results, reduced ICM does not appear to be a precursor of MDD. Future studies should examine ICM in familial high-risk youths across a broad developmental period.

Transforming healthcare delivery: a descriptive study of a novel provider-to-provider virtual care platform.

Introduction: Addressing challenges in access to specialty care, particularly long wait times and geographic disparities, is a pressing issue in the Canadian healthcare system. This study aimed to evaluate the impact and feasibility of provider-to-provider phone consultations between primary care providers (PCPs) and specialists using a novel virtual care platform in Nova Scotia (Virtual Hallway). Methods: We conducted a cross-sectional survey over 5 months, involving 211 PCPs and 34 specialists across Nova Scotia. The survey assessed the need for formal in-person referrals as well as clinician satisfaction. Statistical methods included descriptive statistics and the one-sample t-test. Results: We found that 84% of provider-to-provider phone consultations negated the need for an in-person specialist referral. It was also reported that 90% of patients that did require in-person consultation had enhanced care while they awaited an in-person appointment with a specialist. Very high levels of satisfaction were reported among both PCPs and specialists, and there was a noticeable increase in billing volumes related to these consultations as measured by provincial billing codes. Conclusion: The findings indicate that provider-to-provider phone consultations are feasible, well-accepted and also effective in reducing the need for in-person specialist visits. This approach offers a promising avenue for alleviating waitlist burdens, enhancing the quality of care, and improving the overall efficiency of healthcare delivery.

Association between cannabis use and symptom dimensions in schizophrenia spectrum disorders: an individual participant data meta-analysis on 3053 individuals.

Background: The association between cannabis use and positive symptoms in schizophrenia spectrum disorders is well documented, especially via meta-analyses. Yet, findings are inconsistent regarding negative symptoms, while other dimensions such as disorganization, depression, and excitement, have not been investigated. In addition, meta-analyses use aggregated data discarding important confounding variables which is a source of bias. Methods: PubMed, ScienceDirect and PsycINFO were used to search for publications from inception to September 27, 2022. We contacted the authors of relevant studies to extract raw datasets and perform an Individual Participant Data meta-analysis (IPDMA). Inclusion criteria were: psychopathology of individuals with schizophrenia spectrum disorders assessed by the Positive and Negative Syndrome Scale (PANSS); cannabis-users had to either have a diagnosis of cannabis use disorder or use cannabis at least twice a week. The main outcomes were the PANSS subscores extracted via the 3-factor (positive, negative and general) and 5-factor (positive, negative, disorganization, depression, excitement) structures. Preregistration is accessible via Prospero: ID CRD42022329172. Findings: Among the 1149 identified studies, 65 were eligible and 21 datasets were shared, totaling 3677 IPD and 3053 complete cases. The adjusted multivariate analysis revealed that relative to non-use, cannabis use was associated with higher severity of positive dimension (3-factor: Adjusted Mean Difference, aMD = 0.34, 95% Confidence Interval, CI = [0.03; 0.66]; 5-factor: aMD = 0.38, 95% CI = [0.08; 0.63]), lower severity of negative dimension (3-factor: aMD = -0.49, 95% CI [-0.90; -0.09]; 5-factor: aMD = -0.50, 95% CI = [-0.91; -0.08]), higher severity of excitement dimension (aMD = 0.16, 95% CI = [0.03; 0.28]). No association was found between cannabis use and disorganization (aMD = -0.13, 95% CI = [-0.42; 0.17]) or depression (aMD = -0.14, 95% CI = [-0.34; 0.06]). Interpretation: No causal relationship can be inferred from the current results. The findings could be in favor of both a detrimental and beneficial effect of cannabis on positive and negative symptoms, respectively. Longitudinal designs are needed to understand the role of cannabis is this association. The reported effect sizes are small and CIs are wide, the interpretation of findings should be taken with caution. Funding: This research did not receive any specific grant or funding. Primary financial support for authors was provided by Le Vinatier Psychiatric Hospital.

Addressing Stigma and Promoting Help-Seeking Among African Nova Scotian Youth Experiencing Psychosis and Other Mental Health Problems.

OBJECTIVES: The purpose of this study was to gain an in-depth understanding of perceptions of mental illnesses (especially psychosis), help-seeking, barriers to help-seeking, and opportunities to facilitate help-seeking in the African Nova Scotian Community. METHODS: A qualitative interpretive narrative approach, using the focus group method, was employed to engage African Nova Scotians in discussions on their perceptions and beliefs about mental illnesses and help-seeking in their communities. Youth in Early Intervention services, their caregivers, youth in the community, their caregivers, community leaders, and health service providers, were recruited from four locations in the Halifax Regional Municipality. A total of 75 individuals (37 female, 38 male) participated in the study. Narrative emplotment was used to analyse data from focus groups. RESULTS: Findings from focus groups were categorized based on four areas of discussion: (a) perceptions about psychosis and other mental illnesses among youth, caregivers, service providers and community leaders (b) beliefs about help-seeking among youth, caregivers, services providers and community leaders; (c) barriers and facilitators to seeking help for mental illnesses; and (d) the content and format of educational resources to educate and support youth, families and communities. CONCLUSIONS: Stigma surrounding mental illnesses in the community, lack of knowledge of illness and available services, concerns regarding negative involvement with police, or dismissal of difficulties by health care providers represent significant barriers to help-seeking in this community. Additionally, barriers include a lack of trust in health care services and a dearth of African Nova Scotian service providers. Bolstering capacity of community organizations to support and educate individuals around illness as well as fostering collaboration between health services and community organizations could reduce barriers to care. Future research should focus on examining ways to engage African Nova Scotians in collaboration with existing community organizations.

Neural markers of familial risk for depression - A systematic review.

Structural and functional brain alterations are found in adults with depression. It is not known whether these changes are a result of illness or exist prior to disorder onset. Asymptomatic offspring of parents with depression offer a unique opportunity to research neural markers of familial risk to depression and clarify the temporal sequence between brain changes and disorder onset. We conducted a systematic review to investigate whether asymptomatic offspring at high familial risk have structural and functional brain changes like those reported in adults with depression. Our literature search resulted in 44 studies on 18,645 offspring ranging from 4 weeks to 25 years old. Reduced cortical thickness and white matter integrity, and altered striatal reward processing were the most consistent findings in high-risk offspring across ages. These alterations are also present in adults with depression, suggesting the existence of neural markers of familial risk for depression. Additional studies reproducing current results, streamlining fMRI data analyses, and investigating underexplored topics (i.e intracortical myelin, gyrification, subcortical shape) may be among the next steps required to improve our understanding of neural markers indexing the vulnerability to depression.

Treating Insulin Resistance With Metformin as a Strategy to Improve Clinical Outcomes in Treatment-Resistant Bipolar Depression (the TRIO-BD Study): A Randomized, Quadruple-Masked, Placebo-Controlled Clinical Trial.

Objective: Therapeutic options are limited for treatment-resistant bipolar depression (TRBD). Insulin resistance (IR) confers increased risk for TRBD. We investigated metformin, an insulin sensitizer, to reverse IR and improve clinical outcomes in TRBD.Methods: Using a random-assignment (1:1), intent-to-treat, 2-site, quadruple-masked, parallel-group (metformin to 2,000 mg/d or placebo) clinical trial design, patients with DSM-5 bipolar disorder (BD) type I or II and IR received study medication for 26 weeks (February 2016 to October 2019). The primary outcome was the change in depression rating scores (Montgomery-Asberg Depression Rating Scale [MADRS]) at 14 weeks between those who no longer met IR criteria (converters) and those who still did (non-converters). Additional outcomes included scores on the Global Assessment of Functioning (GAF); the Clinical Global Impressions Scale, Bipolar Disorders version (CGI-BP); and the Hamilton Anxiety Rating Scale (HAM-A) and maintenance of improved outcomes up to 26 weeks.Results: Forty-five BD patients were randomized to metformin (n = 20) or placebo (n = 25), and at 14 weeks or later, 11 subjects no longer met IR criteria (n = 10 with metformin, n = 1 with placebo; P = .0009). These converters experienced significant improvements in MADRS (P values ranged from .031 to .008) and GAF (P values ranged from .045 to .008) scores compared to non-converters beginning at week 6, sustained to week 26. HAM-A (P = .022 at week 14 and .019 at week 26) and CGI-BP change scores (P = .046 at 26 weeks) significantly favored converters over non-converters. Effect sizes were large for the MADRS and GAF (Cohen d > 1 at 14 and 26 weeks) and large for the HAM-A and CGI-BP at 26 weeks. Transient gastrointestinal side effects occurred under both treatment conditions.Conclusions: Pending replication, this early study suggests that reversal of IR by metformin offers a path out of TRBD. Further characterization of metformin converters with TRBD will prove informative.Trial Registration: ClinicalTrials.gov identifier: NCT02519543.

A Retrospective Study of the Clinical Characteristics Associated with Alcohol and Cannabis use in Early Phase Psychosis.

OBJECTIVE: Alcohol and cannabis misuse are common in patients with early phase psychosis (EPP); however, research has tended to focus primarily on cannabis misuse and EPP outcomes, with a relative lack of data on alcohol misuse. This retrospective cross-sectional EPP study investigated the relationship between cannabis, alcohol, and cannabis combined with alcohol misuse, on age, gender, psychotic, depressive and anxiety symptom severity, and social/occupational functioning, at entry to service. METHODS: Two-hundred and sixty-four EPP patients were divided into 4 groups based on substance use measured by the Alcohol, Smoking and Substance Involvement Screening Test: (1) no to low-level cannabis and alcohol misuse (LU), (2) moderate to high alcohol misuse only (AU), (3) moderate to high cannabis misuse only (CU), and (4) moderate to high alcohol and cannabis misuse (AU + CU). RESULTS: We found significant between group differences in age (with the AU group being the oldest and AU + CU group the youngest) as well as gender (with the CU group having the highest percentage of men). There were also group differences in positive psychotic symptoms (lowest in AU group), trait anxiety (highest in AU + CU group), and social/occupational functioning (highest in AU group). Further regression analyses revealed a particularly strong relationship between AU + CU group and trait anxiety (3-fold increased odds of clinical trait anxiety for combined misuse of alcohol and cannabis compared to non/low users). CONCLUSIONS: This study demonstrates the unique demographic and clinical characteristics found in the EPP population at entry to care associated with alcohol and cannabis misuse both separately and in combination. This work highlights the importance of including the assessment of alcohol misuse in addition to cannabis misuse in future treatment guidelines and research.

Microstructural Findings in White Matter Associated with Cannabis and Alcohol Use in Early-Phase Psychosis: A Diffusion Tensor Imaging and Relaxometry Study.

Accumulating evidence suggests that brain white matter (WM) abnormalities may be central to the pathophysiology of psychotic disorders. In addition, there is evidence that cannabis use and alcohol use each is associated with WM abnormalities. However, there are very limited data on the effects of these substances on WM microstructure in patients with psychosis, especially for those at the early phase of illness. This project aimed to examine the impact of cannabis use and alcohol use on WM tissue in early-phase psychosis (EPP). WM was investigated in 21 patients with EPP using diffusion tensor imaging (DTI) and transverse relaxation time of tissue water (T2), with the primary outcomes being mean fractional anisotropy (FA) and T2. DTI analyses were performed at the full-brain level using tract-based spatial statistics with both DTI and T2 analysis done within a WM volume of interest (VOI) implicated in psychosis (containing the left superior longitudinal fasciculus). Our findings revealed that younger age of onset of regular alcohol use (more than one drink per week) was associated with lower FA values in the left thalamic radiation and left parahippocampal and left amygdalar WM. More frequent lifetime cannabis use was correlated with increased mean full-brain FA. There was no significant relationship found between FA and alcohol or cannabis use within the VOI. Relaxometry analysis revealed trend-level evidence of shortened T2 with later onset of regular alcohol use and with more frequent cannabis use. This study provides novel data demonstrating cortical and subcortical WM findings related to alcohol use in EPP and is the first to combine DTI and relaxometry, relating to this patient population.

Integrating Clinical Neurosciences in a Psychiatry Residency Training Program: A Brief Report with Pilot Data.

OBJECTIVE: A novel neuroscience curriculum was developed attempting to address the growing consensus that increased attention be given to incorporating clinical neuroscience in psychiatric residencies. METHODS: Eight 2-h sessions delivered over 2 academic years were incorporated into the teaching curriculum at one institution in which residents participated in case-based clinical neuroscience learning. Each session utilized multimodal teaching methods facilitated by two senior psychiatry residents with support from a faculty mentor. A survey assessing resident comfort with clinical neurosciences was gathered over four timepoints during the 2-year period. RESULTS: There were 69 attendees in total across the four time points, with a 100% response rate to the surveys. There was a significant overall effect found, F(3,16) = 12.64, p < .01, on resident comfort level between the four timepoints. There was a significant increase in comfort level at the third timepoint compared to the first two timepoints; however, there was a notable drop in comfort level between the third and fourth timepoint such that there was no statistically significant difference between the first and last timepoint. Nevertheless, despite mixed positive and negative responses on qualitative analysis, all residents supported the continuation of the course. CONCLUSION: Resident comfort level did not change appreciably with this curriculum; however, there was unanimous support for the continuation of the course in future years. Incorporating this type of curriculum is feasible in a medium-sized psychiatry residency program. Given that subjective comfort ratings are not indicative of actual competency, future work should include objective, competency-based outcomes.

White matter changes in early phase schizophrenia and cannabis use: an update and systematic review of diffusion tensor imaging studies.

OBJECTIVES: The impact of cannabis use on the brain tissue is still unclear, both in the healthy developing brain and in people with schizophrenia. The focus of this review is on white matter, the primary connective infrastructure of the brain. METHODS: We systematically reviewed diffusion tensor imaging (DTI) studies of early phase schizophrenia (illness effect), of cannabis use in otherwise healthy brains (drug effect), and of early phase schizophrenia with cannabis use (combined effects). Studies had to include a healthy, non-cannabis using, control group as well as report on fractional anisotropy as it is the most commonly used DTI index. We excluded cohorts with heavy alcohol or illicit drug use and studies with a sample size of less than 20 in the clinical group. RESULTS: We retained 17 studies of early phase schizophrenia, which together indicate deficits in white matter integrity observed in all fiber tract families, but most frequently in association, callosal and projection fibers. In otherwise healthy cannabis users (2 studies), deficits in white matter tracts were reported mainly in callosal fibers, but also in projection and limbic fibers. In cannabis users with early phase schizophrenia (1 study), deficits in white matter integrity were also observed in all fiber tract families, except for limbic fibers. CONCLUSIONS: The current literature points to several families of white matter tracts being differentially affected in early phase schizophrenia. Further work is required to reveal the impact of cannabis use in otherwise healthy people as well as those with schizophrenia. LIMITATIONS: Paucity of available studies as well as restricting analysis to FA values represent the main limitations of this review.

Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use.

BACKGROUND: A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. METHODS/DESIGN: Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. DISCUSSION: We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding variable of early adolescent onset of regular cannabis use.