Evaluation of the Glymphatic System in Schizophrenia Spectrum Disorder Using Proton Magnetic Resonance Spectroscopy Measurement of Brain Macromolecule and Diffusion Tensor Image Analysis Along the Perivascular Space Index.

BACKGROUND AND HYPOTHESIS: The glymphatic system (GS), a brain waste clearance pathway, is disrupted in various neurodegenerative and vascular diseases. As schizophrenia shares clinical characteristics with these conditions, we hypothesized GS disruptions in patients with schizophrenia spectrum disorder (SCZ-SD), reflected in increased brain macromolecule (MM) and decreased diffusion-tensor-image-analysis along the perivascular space (DTI-ALPS) index. STUDY DESIGN: Forty-seven healthy controls (HCs) and 103 patients with SCZ-SD were studied. Data included 135 proton magnetic resonance spectroscopy (1H-MRS) sets, 96 DTI sets, with 79 participants contributing both. MM levels were quantified in the dorsal-anterior cingulate cortex (dACC), dorsolateral prefrontal cortex, and dorsal caudate (point resolved spectroscopy, echo-time = 35ms). Diffusivities in the projection and association fibers near the lateral ventricle were measured to calculate DTI-ALPS indices. General linear models were performed, adjusting for age, sex, and smoking. Correlation analyses examined relationships with age, illness duration, and symptoms severity. STUDY RESULTS: MM levels were not different between patients and HCs. However, left, right, and bilateral DTI-ALPS indices were lower in patients compared with HCs (P < .001). In HCs, age was positively correlated with dACC MM and negatively correlated with left, right, and bilateral DTI-ALPS indices (P < .001). In patients, illness duration was positively correlated with dACC MM and negatively correlated with the right DTI-ALPS index (P < .05). In the entire population, dACC MM and DTI-ALPS indices showed an inverse correlation (P < .01). CONCLUSIONS: Our results suggest potential disruptions in the GS of patients with SCZ-SD. Improving brain's waste clearance may offer a potential therapeutic approach for patients with SCZ-SD.

Elevated intrinsic cortical curvature in treatment-resistant schizophrenia: Evidence of structural deformation in functional connectivity areas and comparison with alternate indices of structure.

BACKGROUND: Research suggests structural and connectivity abnormalities in patients with treatment-resistant schizophrenia (TRS) compared to first-line responders and healthy-controls. However, measures of these abnormalities are often influenced by external factors like nicotine and antipsychotics, limiting their clinical utility. Intrinsic-cortical-curvature (ICC) presents a millimetre-scale measure of brain gyrification, highly sensitive to schizophrenia differences, and associated with TRS-like traits in early stages of the disorder. Despite this evidence, ICC in TRS remains unexplored. This study investigates ICC as a marker for treatment resistance in TRS, alongside structural indices for comparison. METHODS: We assessed ICC in anterior cingulate, dorsolateral prefrontal, temporal, and parietal cortices of 38 first-line responders, 30 clozapine-resistant TRS, 37 clozapine-responsive TRS, and 52 healthy-controls. For comparative purposes, Fold and Curvature indices were also analyzed. RESULTS: Adjusting for age, sex, nicotine-use, and chlorpromazine equivalence, principal findings indicate ICC elevations in the left hemisphere dorsolateral prefrontal (p < 0.001, η2partial = 0.142) and temporal cortices (LH p = 0.007, η2partial = 0.060; RH p = 0.011, η2partial = 0.076) of both TRS groups, and left anterior cingulate cortex of clozapine-resistant TRS (p = 0.026, η2partial = 0.065), compared to healthy-controls. Elevations that correlated with reduced cognition (p = 0.001) and negative symptomology (p < 0.034) in clozapine-resistant TRS. Fold and Curvature indices only detected group differences in the right parietal cortex, showing interactions with age, sex, and nicotine use. ICC showed interactions with age. CONCLUSION: ICC elevations were found among patients with TRS, and correlated with symptom severity. ICCs relative independence from sex, nicotine-use, and antipsychotics, may support ICC's potential as a viable marker for TRS, though age interactions should be considered.

Assessing past suicidal behaviour in schizophrenia spectrum disorders using the Columbia-Suicide Severity Rating Scale and the Beck Scale for Suicide Ideation: Analysis across the life-span.

Assessing the number of past suicide attempts is vital in clinical and research settings, as it is a significant variable in assessing suicide risk. This study sought to compare the accuracy of the C-SSRS and the BSS in reporting past suicide attempts in schizophrenia spectrum disorders . Six hundred participants were recruited from the Centre for Addiction and Mental Health in Toronto, and completed the BSS and C-SSRS. A medical chart review was performed to determine the number of past suicide attempts. In addition, receiver operating characteristic curves were generated to compare the accuracy of both tests under various stratifications. Based on our findings, there were no significant differences (P = 0.8977) between the BSS and CSSRS in detecting a history of past suicide attempts. The BSS exhibited a sensitivity of 0.847 and a specificity of 0.841, while the C-SSRS had a slightly lower sensitivity of 0.795 and a slightly higher specificity of 0.889. Additionally, repeating the analysis to determine the accuracy of detecting multiple past suicide attempts, the BSS demonstrated a sensitivity of 0.704 and a specificity of 0.959, whereas the C-SSRS had a sensitivity of 0.787 and a specificity of 0.927. We further contrasted the two scales, stratified by different demographic variables such as age and sex. The accuracy of both tools, which is defined as the ability to identify true positive cases while minimizing false positives, increased as age increased, but these differences were not statistically significant. Therefore, both tools show a high level of accuracy in reporting past suicide attempt history and should be utilized to fit the specific needs of the research or clinical teams. These findings can inform clinical practice and future research, highlighting the importance of selecting assessment tools that fit the population's needs and context.

Disease Progression Patterns of Brain Morphology in Schizophrenia: More Progressed Stages in Treatment Resistance.

BACKGROUND AND HYPOTHESIS: Given the heterogeneity and possible disease progression in schizophrenia, identifying the neurobiological subtypes and progression patterns in each patient may lead to novel biomarkers. Here, we adopted data-driven machine-learning techniques to identify the progression patterns of brain morphological changes in schizophrenia and investigate the association with treatment resistance. STUDY DESIGN: In this cross-sectional multicenter study, we included 177 patients with schizophrenia, characterized by treatment response or resistance, with 3D T1-weighted magnetic resonance imaging. Cortical thickness and subcortical volumes calculated by FreeSurfer were converted into z scores using 73 healthy controls data. The Subtype and Stage Inference (SuStaIn) algorithm was used for unsupervised machine-learning analysis. STUDY RESULTS: SuStaIn identified 3 different subtypes: (1) subcortical volume reduction (SC) type (73 patients), in which volume reduction of subcortical structures occurs first and moderate cortical thinning follows, (2) globus pallidus hypertrophy and cortical thinning (GP-CX) type (42 patients), in which globus pallidus hypertrophy initially occurs followed by progressive cortical thinning, and (3) cortical thinning (pure CX) type (39 patients), in which thinning of the insular and lateral temporal lobe cortices primarily happens. The remaining 23 patients were assigned to baseline stage of progression (no change). SuStaIn also found 84 stages of progression, and treatment-resistant schizophrenia showed significantly more progressed stages than treatment-responsive cases (P = .001). The GP-CX type presented earlier stages than the pure CX type (P = .009). CONCLUSIONS: The brain morphological progressions in schizophrenia can be classified into 3 subtypes, and treatment resistance was associated with more progressed stages, which may suggest a novel biomarker.

Copy Number Variation Analysis of Aggressive Behaviour in Schizophrenia.

INTRODUCTION: An increased proclivity towards violence is often associated with those diagnosed with schizophrenia (SCZ), despite contradictory findings from prior studies exploring the association between violence and SCZ. Evidence has shown that certain comorbidities, specifically the presence of a substance use disorders, can result in increased aggression in those with SCZ. Copy number variation (CNV) load has also previously been implicated in the genetic vulnerability of individuals with SCZ. For this study, we aimed to determine whether CNV load correlates with increased violence in SCZ. METHODS: Community-dwelling patients diagnosed with SCZ spectrum disorders (n = 203) were recruited from a non-forensic population. The assessment for aggression was completed using a cross-sectional and retrospective design, and CNV analysis was conducted analysing genomic DNA using the Illumina Omni 2.5 array. RESULTS: No correlation between the number of CNV events (either deletion or duplication) and the severity of the physical violence episode index was found. However, there was a significant association between larger deletion events across the violent behaviours under investigation. DISCUSSION: These results need to be confirmed in more extensive studies using standardized tools developed for non-forensic populations, such as the Brown-Goodwin Scale of Aggression.

GABAergic signaling in alcohol use disorder and withdrawal: pathological involvement and therapeutic potential.

Alcohol is one of the most widely used substances. Alcohol use accounts for 5.1% of the global disease burden, contributes substantially to societal and economic costs, and leads to approximately 3 million global deaths yearly. Alcohol use disorder (AUD) includes various drinking behavior patterns that lead to short-term or long-lasting effects on health. Ethanol, the main psychoactive molecule acting in alcoholic beverages, directly impacts the GABAergic system, contributing to GABAergic dysregulations that vary depending on the intensity and duration of alcohol consumption. A small number of interventions have been developed that target the GABAergic system, but there are promising future therapeutic avenues to explore. This review provides an overview of the impact of alcohol on the GABAergic system, the current interventions available for AUD that target the GABAergic system, and the novel interventions being explored that in the future could be included among first-line therapies for the treatment of AUD.

Characterization and prediction of individual functional outcome trajectories in schizophrenia spectrum disorders (PREDICTS study): Study protocol.

Schizophrenia spectrum disorders (SSDs) are associated with significant functional impairments, disability, and low rates of personal recovery, along with tremendous economic costs linked primarily to lost productivity and premature mortality. Efforts to delineate the contributors to disability in SSDs have highlighted prominent roles for a diverse range of symptoms, physical health conditions, substance use disorders, neurobiological changes, and social factors. These findings have provided valuable advances in knowledge and helped define broad patterns of illness and outcomes across SSDs. Unsurprisingly, there have also been conflicting findings for many of these determinants that reflect the heterogeneous population of individuals with SSDs and the challenges of conceptualizing and treating SSDs as a unitary categorical construct. Presently it is not possible to identify the functional course on an individual level that would enable a personalized approach to treatment to alter the individual's functional trajectory and mitigate the ensuing disability they would otherwise experience. To address this ongoing challenge, this study aims to conduct a longitudinal multimodal investigation of a large cohort of individuals with SSDs in order to establish discrete trajectories of personal recovery, disability, and community functioning, as well as the antecedents and predictors of these trajectories. This investigation will also provide the foundation for the co-design and testing of personalized interventions that alter these functional trajectories and improve outcomes for people with SSDs.

Dynamic change in genome-wide methylation in response to increased suicidal ideation in schizophrenia spectrum disorders.

Suicide is a significant public health crisis, with 800,000 people dying annually. Most people completing suicide have previous psychiatric conditions, and those with psychotic and mood disorders are particularly vulnerable. Unfortunately, there are currently no biomarkers available for accurately detecting suicidal ideation. Given the genetic and environmental factors that play a role in suicidal ideation, we attempted to determine epigenetic modifications, specifically DNA methylation, in response to changes in suicidal ideation. Using a longitudinal study design, 31 participants with schizophrenia spectrum disorders were interviewed at a baseline visit and again at a follow-up visit 3-12 months later. Current suicidal ideation was recorded at both visits with the Columbia Suicide Severity Rating Scale and the Beck Scale for Suicide Ideation, and whole blood was collected for methylation analysis. Our analysis shows a significant negative correlation between cg26910920 methylation and increasing Columbia Suicide Severity Rating Scale scores and a positive correlation between cg13673029 methylation and increasing Beck Scale for Suicide Ideation scores. This pilot study indicates that there is  the possibility  that DNA methylation can respond to changes in suicidal ideation over time and potentially be used as a biomarker of suicidal ideation in the future.

Insight in schizophrenia is associated with psychoeducation and social support: Testing a new more comprehensive insight tool in Turkish schizophrenia patients.

Insight is a continuous and multidimensional phenomenon, including awareness of having an illness, the presence of symptoms and accurate symptom attribution, the need for treatment, and the consequences of treatment. Good insight into illness is associated with better adherence to treatment, better cognitive, psychosocial, and vocational functioning along with less symptom severity, decreased relapses, and hospitalizations. Several tools are used for insight evaluation. We recruited 90 patients diagnosed with schizophrenia and analyzed the forms of 58 patients. The patients completed the VAGUS-SR (self-rated), Beck Cognitive Insight Scale, Knowledge About Schizophrenia Questionnaire, and Multidimensional Scale of Perceived Social Support (MSPSS). Clinicians performed a mental status examination and completed the Positive and Negative Syndrome Scale, Schedule for the Assessment of Insight, VAGUS-CR (clinician-rated), Calgary Depression Scale for Schizophrenia, and Clinical Global Impressions. We found that the level of insight evaluated using the VAGUS forms increased with knowledge regarding schizophrenia. Upon investigating the relationship between perceived social support and insight, we identified a relationship between VAGUS-CR and only significant other subscales of MSPSS, and between one of the VAGUS-SR scale sub-dimensions and significant other and total scores of MSPSS. Our findings also suggest that the VAGUS-SR and VAGUS-CR scales can be used to evaluate insight in Turkish populations. The positive relationship between perceived social support and insight emphasizes the importance of increasing social support through interventions aimed at improving insight. Our data also highlighted the value of psychoeducational studies in this patient group. Considering the multidimensional effects of insight on patients with schizophrenia, it would be beneficial to use scales such as VAGUS, which allow the insights of individuals to be evaluated in detail by both the clinician and the patient.

GWAS of biological aging to find longevity genes in schizophrenia.

Schizophrenia (SCZ) is a severe psychotic disorder associated with premature mortality and aging. Moreover, the symptoms and progression of psychiatric disorders in general are associated with decreased lifespan, biological aging, and poorer medical outcomes. In this study, we investigated the relationship between several epigenetic clocks and scanned the entire genome for association in a cohort of SCZ individuals (n = 107). Biological age was computed from blood DNA methylation (DNAm) and tested for association against  common  variants across the genome using general linear models. Genes affecting epigenetic age acceleration in our cohort were found mainly when using the telomeric length clock rather than the other biological clocks. These findings pair with existing evidence that there are some genes associated with longevity and suggest further investigations of  putative biological mechanisms for morbidity and premature mortality, not only in patients with SCZ but also in the general population.

Outcomes and clinical implications of intranasal insulin on cognition in humans: A systematic review and meta-analysis.

BACKGROUND: Aberrant brain insulin signaling has been posited to lie at the crossroads of several metabolic and cognitive disorders. Intranasal insulin (INI) is a non-invasive approach that allows investigation and modulation of insulin signaling in the brain while limiting peripheral side effects. OBJECTIVES: The objective of this systematic review and meta-analysis is to evaluate the effects of INI on cognition in diverse patient populations and healthy individuals. METHODS: MEDLINE, EMBASE, PsycINFO, and Cochrane CENTRAL were systematically searched from 2000 to July 2021. Eligible studies were randomized controlled trials that studied the effects of INI on cognition. Two independent reviewers determined study eligibility and extracted relevant descriptive and outcome data. RESULTS: Twenty-nine studies (pooled N = 1,726) in healthy individuals as well as those with Alzheimer's disease (AD)/mild cognitive impairment (MCI), mental health disorders, metabolic disorders, among others, were included in the quantitative meta-analysis. Patients with AD/MCI treated with INI were more likely to show an improvement in global cognition (SMD = 0.22, 95% CI: 0.05-0.38 p = <0.00001, N = 12 studies). Among studies with healthy individuals and other patient populations, no significant effects of INI were found for global cognition. CONCLUSIONS: This review demonstrates that INI may be associated with pro-cognitive benefits for global cognition, specifically for individuals with AD/MCI. Further studies are required to better understand the neurobiological mechanisms and differences in etiology to dissect the intrinsic and extrinsic factors contributing to the treatment response of INI.

Metabolomic signatures associated with weight gain and psychosis spectrum diagnoses: A pilot study.

Psychosis spectrum disorders (PSDs), as well as other severe mental illnesses where psychotic features may be present, like bipolar disorder, are associated with intrinsic metabolic abnormalities. Antipsychotics (APs), the cornerstone of treatment for PSDs, incur additional metabolic adversities including weight gain. Currently, major gaps exist in understanding psychosis illness biomarkers, as well as risk factors and mechanisms for AP-induced weight gain. Metabolomic profiles may identify biomarkers and provide insight into the mechanistic underpinnings of PSDs and antipsychotic-induced weight gain. In this 12-week prospective naturalistic study, we compared serum metabolomic profiles of 25 cases within approximately 1 week of starting an AP to 6 healthy controls at baseline to examine biomarkers of intrinsic metabolic dysfunction in PSDs. In 17 of the case participants with baseline and week 12 samples, we then examined changes in metabolomic profiles over 12 weeks of AP treatment to identify metabolites that may associate with AP-induced weight gain. In the cohort with pre-post data (n = 17), we also compared baseline metabolomes of participants who gained ≥5% baseline body weight to those who gained <5% to identify potential biomarkers of antipsychotic-induced weight gain. Minimally AP-exposed cases were distinguished from controls by six fatty acids when compared at baseline, namely reduced levels of palmitoleic acid, lauric acid, and heneicosylic acid, as well as elevated levels of behenic acid, arachidonic acid, and myristoleic acid (FDR < 0.05). Baseline levels of the fatty acid adrenic acid was increased in 11 individuals who experienced a clinically significant body weight gain (≥5%) following 12 weeks of AP exposure as compared to those who did not (FDR = 0.0408). Fatty acids may represent illness biomarkers of PSDs and early predictors of AP-induced weight gain. The findings may hold important clinical implications for early identification of individuals who could benefit from prevention strategies to reduce future cardiometabolic risk, and may lead to novel, targeted treatments to counteract metabolic dysfunction in PSDs.

Cortical thinning in relation to impaired insight into illness in patients with treatment resistant schizophrenia.

Impaired insight into illness is a common element of schizophrenia that contributes to treatment nonadherence and negative clinical outcomes. Previous studies suggest that impaired insight may arise from brain abnormalities. However, interpretations of these findings are limited due to small sample sizes and inclusion of patients with a narrow range of illness severity and insight deficits. In a large sample of patients with schizophrenia, the majority of which were designated as treatment-resistant, we investigated the associations between impaired insight and cortical thickness and subcortical volumes. A total of 94 adult participants with a schizophrenia spectrum disorder were included. Fifty-six patients (60%) had treatment-resistant schizophrenia. The core domains of insight were assessed with the VAGUS insight into psychosis scale. We obtained 3T MRI T1-weighted images, which were analysed using CIVET and MAGeT-Brain. Whole-brain vertex-wise analyses revealed impaired insight, as measured by VAGUS average scores, was related to cortical thinning in left frontotemporoparietal regions. The same analysis in treatment-resistant patients showed thinning in the same regions, even after controlling for age, sex, illness severity, and chlorpromazine antipsychotic dose equivalents. No association was found in non-treatment-resistant patients. Region-of-interest analyses revealed impaired general illness awareness was associated with cortical thinning in the left supramarginal gyrus when controlling for covariates. Reduced right and left thalamic volumes were associated with VAGUS symptom attribution and awareness of negative consequences subscale scores, respectively, but not after correction for multiple testing. Our results suggest impaired insight into illness is related to cortical thinning in left frontotemporoparietal regions in patients with schizophrenia, particularly those with treatment resistance where insight deficits may be more chronic.

Mediating effect of genome-wide DNA methylation on suicidal ideation induced by stressful events.

OBJECTIVE: Schizophrenia is a debilitating disease that is associated with higher rates of death by unnatural causes including suicide. Exposure to stressful events is an important risk factor for suicidal ideation (SI); however, the mechanisms that link stress, SI, and suicide remain unclear. Epigenetic processes are involved in both vulnerability to suicidal behavior and stress. Therefore, we sought to study the relationship between epigenetic modifications and suicidal behavior and stress. METHODS: This pilot study was conducted on 39 patients diagnosed with schizophrenia (54% men and age 45.5 ± 12.7). We analyzed the effects of (a) stress exposure and (b) the mediation of DNA methylation [via an epigenetic wide association study (EWAS) of more than 450 000 CpG sites across the genome] on SI severity. RESULTS: The top CpG site mediating the effect of global stress exposure on SI was cg27660192 located in an intergenic region on chromosome 11, exerting a facilitating effect on worsening SI through DNA hypomethylation. CONCLUSION: These preliminary results indicate that DNA methylation in peripheral tissues can shed light on the complex relationship between stress and SI in schizophrenia.

Genome-wide methylation analysis of treatment resistant schizophrenia.

Various studies have investigated the relationship between genetic polymorphisms of antipsychotic drug-metabolizing agents and drug response. DNA methylation is a form of epigenetic modification that regulates gene expression. Few studies have analyzed the relationship between genome-wide methylation patterns and treatment resistance schizophrenia. The primary aim of this pilot study is to investigate the association between treatment resistance status and genome-wide DNA methylation in schizophrenia patients. Treatment resistance status was determined for 109 patients with schizophrenia. Treatment resistance was the primary outcome variable in a model, including methylation status of white blood cells using the Illumina 450 array. The genome-wide DNA methylation levels in 109 Schizophrenia subjects did not show that DNA methylation sties were associated with resistance status. From our study, it is evident the importance of continuing to investigate the relationship between DNA methylation and antipsychotic response to personalize treatment in schizophrenia. Future studies require larger prescription databases to build on the results presented in this pilot study.

Residual or re-emergent impaired insight into delusions following remission is unrelated to later relapse during a randomized clinical trial of continuation pharmacotherapy for psychotic depression - The STOP-PD II Study.

BACKGROUND: Impaired insight into delusions is associated with a lower probability of remission of psychotic depression, independent of illness severity. The relationship between participant characteristics and impaired insight into delusions in remitted psychotic depression, and whether impaired insight is associated with risk of relapse of psychotic depression during continuation pharmacotherapy were examined. METHODS: Data were analyzed from 126 participants in the STOP-PD II study who experienced sustained remission of psychotic depression during 8-week stabilization treatment with sertraline plus olanzapine and were then randomized to 36 weeks of continuation treatment with sertraline plus either olanzapine or placebo. Insight into delusions was assessed with the Resolution of Delusions Scale (RODS). Linear regression analyses examined the associations between participant characteristics and insight into delusions. Cox proportional-hazards models examined whether i) change in RODS during stabilization treatment; or ii) RODS at the end of stabilization treatment predicted risk of relapse during 36 weeks of continuation treatment. RESULTS: Severity of psychosis before initiation of treatment was the only participant characteristic associated with the change in insight during stabilization treatment. Neither change in insight during stabilization treatment nor insight at the end of stabilization treatment was associated with risk of relapse. LIMITATIONS: Insufficient statistical power and the lack of variability in RODS scores at the time of randomization may have contributed to the absence of a relationship between RODS and risk of relapse. CONCLUSION: Residual or reemergent insight impairment following acute treatment does not preclude patients from sustaining remission of psychotic depression in a randomized placebo-controlled trial.

Technology-Enabled Collaborative Care for Concurrent Diabetes and Distress Management During the COVID-19 Pandemic: Protocol for a Mixed Methods Feasibility Study.

BACKGROUND: The COVID-19 pandemic disrupted the delivery of diabetes care and worsened mental health among many patients with type 2 diabetes (T2D). This disruption puts patients with T2D at risk for poor diabetes outcomes, especially those who experience social disadvantage due to socioeconomic class, rurality, or ethnicity. The appropriate use of communication technology could reduce these gaps in diabetes care created by the pandemic and also provide support for psychological distress. OBJECTIVE: The purpose of this study is to test the feasibility of an innovative co-designed Technology-Enabled Collaborative Care (TECC) model for diabetes management and mental health support among adults with T2D. METHODS: We will recruit 30 adults with T2D residing in Ontario, Canada, to participate in our sequential explanatory mixed methods study. They will participate in 8 weekly web-based health coaching sessions with a registered nurse, who is a certified diabetes educator, who will be supported by a digital care team (ie, a peer mentor, an addictions specialist, a dietitian, a psychiatrist, and a psychotherapist). Assessments will be completed at baseline, 4 weeks, and 8 weeks, with a 12-week follow-up. Our primary outcome is the feasibility and acceptability of the intervention, as evident by the participant recruitment and retention rates. Key secondary outcomes include assessment completion and delivery of the intervention. Exploratory outcomes consist of changes in mental health, substance use, and physical health behaviors. Stakeholder experience and satisfaction will be explored through a qualitative descriptive study using one-on-one interviews. RESULTS: This paper describes the protocol of the study. The recruitment commenced in June 2021. This study was registered on October 29, 2020, on ClinicalTrials.gov (Registry ID: NCT04607915). As of June 2022, all participants have been recruited. It is anticipated that data analysis will be complete by the end of 2022, with study findings available by the end of 2023. CONCLUSIONS: The development of an innovative, technology-enabled model will provide necessary support for individuals living with T2D and mental health challenges. This TECC program will determine the feasibility of TECC for patients with T2D and mental health issues. TRIAL REGISTRATION: ClinicalTrials.gov NCT04607915; https://clinicaltrials.gov/ct2/show/NCT04607915. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39724.

Concordance between the Columbia-Suicide Severity Rating Scale and Beck Scale for Suicide Ideation in assessing suicide behaviour in young adults with schizophrenia spectrum disorders.

The Columbia Suicide Severity Rating Scale (C-SSRS) is considered the gold standard for collecting information on suicidal ideation and behavior by the Food and Drug Administration (FDA) of the United States. To determine the accuracy of the C-SSRS compared to the Beck Scale for Suicidal Ideation (BSS) for collecting suicide attempt history in the schizophrenia population, 202 participants aged 18-40 with schizophrenia spectrum disorders were administered the C-SSRS, followed by the BSS. Medical charts were reviewed to confirm the lifetime history of actual suicide attempts. The BSS had an 83.5% accuracy in reporting single suicide attempts and 81.7% for multiple suicide attempts; while the C-SSRS had 84.1% and 83.9% accuracy respectively. This difference was not statistically significant (p = 0.849). Both the BSS and C-SSRS demonstrated high sensitivity and specificity in collecting suicide attempt history for young patients with psychosis, with no significant differences. Future investigators may choose the scale that is best suited to the level of detail required.

Self- versus informant-report of cognitive decline in mild cognitive impairment: Concordance with cognitive and functional performance.

OBJECTIVE: Debate continues regarding the use of self- versus informant-report to diagnose mild cognitive impairment (MCI) with studies reporting patients both overestimating and underestimating their abilities relative to informants. We assessed concordance of self- versus informant-report of cognitive decline with objective cognitive and functional performance in the participants of the preventing Alzheimer's dementia with cognitive remediation plus transcranial direct current stimulation in mild cognitive impairment and depression randomized controlled trial (PACt-MD). METHOD: Three hundred six participants with MCI, and their informants, reported on cognitive decline; the participants also completed a comprehensive assessment of objective cognitive and functional performance. Based on the discrepancy between self- versus informant-report of cognitive decline, we grouped participants into categories of underestimators, congruent estimators, and overestimators. RESULTS: Informant- but not self-reported cognitive decline significantly correlated with objective cognitive performance. There were 68 underestimators, 94 congruent estimators, and 144 overestimators. Underestimators had significantly lower objective cognitive performance and functional performance than congruent estimators and overestimators. Cognitive performance significantly predicted functional performance in all three groups, and the relationship between cognitive and functional performance was moderated by the discrepancy between self- and informant-report. CONCLUSIONS: We showed a poor concordance among self-report of cognitive decline and both informant-report of cognitive decline and cognitive performance in patients with MCI. Our findings highlight clinical and research value in the assessment and consideration of degree of discrepancy between self- and informant-reports of cognitive decline in MCI. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Decreased cortical gyrification and surface area in the left medial parietal cortex in patients with treatment-resistant and ultratreatment-resistant schizophrenia.

AIM: Validating the vulnerabilities and pathologies underlying treatment-resistant schizophrenia (TRS) is an important challenge in optimizing treatment. Gyrification and surface area (SA), reflecting neurodevelopmental features, have been linked to genetic vulnerability to schizophrenia. The aim of this study was to identify gyrification and SA abnormalities specific to TRS. METHODS: We analyzed 3T magnetic resonance imaging findings of 24 healthy controls (HCs), 20 responders to first-line antipsychotics (FL-Resp), and 41 patients with TRS, including 19 clozapine responders (CLZ-Resp) and 22 FL- and clozapine-resistant patients (patients with ultratreatment-resistant schizophrenia [URS]). The local gyrification index (LGI) and associated SA were analyzed across groups. Diagnostic accuracy was verified by receiver operating characteristic curve analysis. RESULTS: Both CLZ-Resp and URS had lower LGI values than HCs (P = 0.041, Hedges g [gH ] = 0.75; P = 0.013, gH  = 0.96) and FL-Resp (P = 0.007, gH  = 1.00; P = 0.002, gH  = 1.31) in the left medial parietal cortex (Lt-MPC). In addition, both CLZ-Resp and URS had lower SA in the Lt-MPC than FL-Resp (P < 0.001, gH  = 1.22; P < 0.001, gH  = 1.75). LGI and SA were positively correlated in non-TRS (FL-Resp) (ρ = 0.64, P = 0.008) and TRS (CLZ-Resp + URS) (ρ = 0.60, P < 0.001). The areas under the receiver operating characteristic curve for non-TRS versus TRS with LGI and SA in the Lt-MPC were 0.79 and 0.85, respectively. SA in the Lt-MPC was inversely correlated with negative symptoms (ρ = -0.40, P = 0.018) and clozapine plasma levels (ρ = -0.35, P = 0.042) in TRS. CONCLUSION: LGI and SA in the Lt-MPC, a functional hub in the default-mode network, were abnormally reduced in TRS compared with non-TRS. Thus, altered LGI and SA in the Lt-MPC might be structural features associated with genetic vulnerability to TRS.