Neurocognitive correlates of metabolic dysregulation in individuals with mood disorders: a systematic review and meta-analysis.

Individuals with mood disorders are predisposed to metabolic dysfunction, while those with metabolic dysregulation such as diabetes and obesity experience more severe depressive symptoms. Both metabolic dysfunction and mood disorders are independently associated with cognitive deficits. Therefore, given their close association, this study aimed to explore the association between metabolic dysfunction in individuals with mood disorders in relation to cognitive outcomes. A comprehensive search comprised of these three domains was carried out; a random-effects meta-analysis pooling mean cognitive outcomes was conducted (PROSPERO ID: CRD42022295765). Sixty-three studies were included in this review; 26 were synthesized in a quantitative meta-analysis. Comorbid metabolic dysregulation was associated with significantly lower global cognition among individuals with mood disorders. These trends were significant within each mood disorder subgroup, including major depressive disorder, bipolar disorder, and self-report depression/depressive symptoms. Type 2 diabetes was associated with the lowest cognitive performance in individuals with mood disorders, followed by peripheral insulin resistance, body mass index ⩾25 kg/m2, and metabolic syndrome. Significant reduction in scores was also observed among individual cognitive domains (in descending order) of working memory, attention, executive function, processing speed, verbal memory, and visual memory. These findings demonstrate the detrimental effects of comorbid metabolic dysfunction in individuals with mood disorders. Further research is required to understand the underlying mechanisms connecting mood disorders, metabolism, and cognition.

Promising translatable pharmacological interventions for body weight management in individuals with severe mental illness - a narrative review.

INTRODUCTION: Psychotropic medications, especially antipsychotics, have been consistently shown to cause weight gain in individuals with severe mental illness (SMI), a population inherently challenged by poor physical health. Consequently, compared to the general population, this contributes to an increased cardiometabolic burden, including the risk of type 2 diabetes, dyslipidemia, and hypertension. Furthermore, comorbid obesity leads to treatment nonadherence, decreased quality of life, and increased risk of relapse, posing a challenge in the management of mental health. To address this, emerging agents investigated in the general population with potential to mitigate weight gain were explored to assess translatability to the SMI population. AREAS COVERED: A literature search was conducted including agents approved for the management of obesity in the general population, along with upcoming agents under investigation in phase III trials with weight loss properties. EXPERT OPINION: Metformin and topiramate along with lifestyle interventions are commonly prescribed for weight gain in individuals with SMI; however, their weight loss potential is modest at best. This review identified tirzepatide and cagrilintide-semaglutide among others as promising agents for adjunctive pharmacological management of weight gain.

Semaglutide for the treatment of antipsychotic-associated weight gain in patients not responding to metformin - a case series.

Metformin is the currently accepted first-line treatment for antipsychotic-associated weight gain (AAWG). However, not all patients benefit from metformin. Glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown promise in the management of obesity in the general population, with preliminary evidence supporting efficacy in AAWG. Semaglutide is a weekly injectable GLP-1RA which received recent approval for obesity management and noted superiority over other GLP-1RAs. This study explored the efficacy and tolerability of semaglutide in AAWG among individuals with severe mental illness. A retrospective chart review of patients treated with semaglutide in the Metabolic Clinic at the Center for Addiction and Mental Health (CAMH) between 2019 and 2021 was conducted. Patients failing a trial of metformin (<5% weight loss or continuing to meet criteria for metabolic syndrome) after 3 months at the maximum tolerated dose (1500-2000 mg/day) were initiated on semaglutide up to 2 mg/week. The primary outcome measure was a change in weight at 3, 6, and 12 months. Twelve patients on weekly semaglutide injections of 0.71 ± 0.47 mg/week were included in the analysis. About 50% were female; the average age was 36.09 ± 13.32 years. At baseline, mean weight was 111.4 ± 31.7 kg, BMI was 36.7 ± 8.2 kg/m2, with a mean waist circumference of 118.1 ± 19.3 cm. A weight loss of 4.56 ± 3.15 kg (p < 0.001), 5.16 ± 6.27 kg (p = 0.04) and 8.67 ± 9 kg (p = 0.04) was seen at 3, 6, and 12 months, respectively, after initiation of semaglutide with relatively well-tolerated side-effects. Initial evidence from our real-world clinical setting suggests that semaglutide may be effective in reducing AAWG in patients not responding to metformin. Randomized control trials investigating semaglutide for AAWG are needed to corroborate these findings.

Impact of deep vein thrombosis on adolescent athletes: Navigating an invisible disability.

Background: Injury in adolescent athletes that threatens their sport participation can result in a sense of identity loss during critical years for identity development, creating the potential for significant mental health challenges. The specific effect of deep vein thrombosis (DVT) in this vulnerable population has not been characterized. Purpose: To describe the impact of DVT diagnosis, treatment, and long-term complications on the mental well-being of athletes who sustained a DVT during adolescence and to identify strategies to improve the quality of care for these patients. Methods: Using a qualitative study design, athletes with a history of DVT during adolescence and their parents were recruited to participate in semistructured interviews. Interviews were transcribed and analyzed using thematic analysis. Participants were recruited until reaching thematic saturation. Results: In total, 19 participants (12 athletes, 7 parents) were recruited. Athletes were mainly males (67%), median age at time of DVT was 15 years (range, 12-18 years), and median age at study participation was 19 years (range, 16-34 years). Thematic analysis revealed four main themes: Theme 1: DVT posed a threat to sport participation; Theme 2: at a personal level, there were significant mental health challenges; Theme 3: at a societal level, DVT is an invisible disability; and Theme 4: physical, psychological, and transition support are important to improve the care of these patients. Conclusion: Deep vein thrombosis threatens an athlete's participation in sport, resulting in a significant and complex impact on their mental well-being. Heightened awareness and a multidisciplinary approach are needed to help young athletes navigate the consequences of DVT.

The metabolic adverse effects of antipsychotic use in individuals with intellectual and/or developmental disability: A systematic review and meta-analysis.

OBJECTIVE: Individuals with intellectual and/or developmental disability (IDD) are often prescribed antipsychotics (APs). However, despite their known propensity to cause metabolic adverse effects, including weight gain, diabetes, and increased risk of cardiovascular events, there is currently a limited body of literature describing the metabolic consequences of AP use in this population. METHODS: We searched MEDLINE, EMBASE, PsychINFO, CENTRAL, and CINAHL databases to identify all randomized trials that reported on the metabolic effects of APs in individuals with IDD. Random effects meta-analyses were used to examine weight gain as both a continuous and dichotomous outcome. RESULTS: Eighteen randomized trials met our inclusion criteria with a total of 1376 patients across a variety of IDDs. AP use was associated with significantly greater weight gain compared with placebo (Continuous: mean difference = 1.10 kg, [0.79, 1.40], p < 0.00001, I2  = 54%; Dichotomous: odds ratio = 3.94, [2.15, 7.23], p < 0.00001, I2  = 0). Sub-group analysis revealed no significant effect of AP type. Data regarding the effects of APs on other metabolic outcomes were limited. CONCLUSION: This review (PROSPERO # CRD42021255558) demonstrates that AP use is associated with significant weight gain among patients with IDD. Concerningly, most reported studies were in children and adolescents, which sets up an already vulnerable population for adverse medical sequalae at an early age. There was also a lack of long-term studies in adults with IDD. Further studies are required to better understand how AP use affects metabolic parameters in this group of individuals.

Characteristics of upper- and lower-extremity deep vein thrombosis and predictors of postthrombotic syndrome in children.

Our understanding of postthrombotic syndrome (PTS) predictors in children is evolving. The present study aimed to investigate differences in patient- and deep vein thrombosis (DVT)-related characteristics between central venous catheter (CVC)-related and non-CVC-related thrombosis in children, as well as early PTS predictors. Children aged 0 to 18 years were prospectively recruited ≥6 months after imaging-proven upper- or lower-extremity DVT. PTS was measured using CAPTSure. Early predictors included age at DVT diagnosis, DVT symptoms, DVT burden, and days on therapeutic anticoagulation within 30 days post-DVT diagnosis. Analysis of predictors was stratified by CVC-related and non-CVC-related thrombosis. Generalized estimating equations were used for data analyses. In total, 313 DVT-affected extremities of 256 patients were assessed; 275 (88%) DVT cases were CVC related. Patients with non-CVC-related thrombosis were older (median age, 5.8 years; 25th-75th percentile, 4.9-6.4 years vs 3.5 months; 25th-75th percentile, 0.7-18.7 months; P < .001) and more likely to have thrombophilia (64% vs 22%; P < .001) and obesity (30% vs 13%; P = .01) than patients with CVC-related thrombosis. CAPTSure scores were 9.5 points higher (standard error, 3.0; P = .02) in the non-CVC-related thrombosis stratum. Age at the time of DVT predicted PTS in both strata; DVT burden and time from DVT diagnosis to PTS assessment predicted PTS in CVC-related thrombosis. In sum, PTS severity was higher in non-CVC-related vs CVC-related thrombosis. Increasing age at the time of DVT was associated with higher PTS severity. DVT burden and time from DVT diagnosis to PTS assessment were significant PTS predictors in CVC-related thrombosis, indicating that long-term follow-up of these children is important.

Compression garments for the management of pediatric post-thrombotic syndrome: A prospective longitudinal study.

BACKGROUND: Graduated compression garments (CG) are a standard form of management of post-thrombotic syndrome (PTS) in adults, but data in children are lacking. OBJECTIVES: We aimed to study the attitudes toward CG and change in PTS severity score in children who were prescribed CG for PTS management. METHODS: Children with PTS were enrolled in this longitudinal prospective study at the time of CG prescription. PTS severity was measured at baseline and follow-up using CAPTSure© ; attitude toward CG was registered at follow-up. RESULTS: Forty-five patients were enrolled (median age 13 years, 25th-75th percentile 8-15 years; 53% male patients); 71% were prescribed socks and 29% sleeves; pressure was 15-20 mmHg in 84% of CG. Median baseline PTS CAPTSure© score was 31 points (25th-75th percentile 21-45 points). At follow-up, 49% of patients found CG helpful, 27% found CG not helpful, and 16% did not buy or wear the CG. Eight percent of enrolled patients did not return for study follow-up. Ninety-five percent of the children who found CG helpful wore them for ≥3 days/week. Hours of CG wear at the time of follow-up were associated with lower PTS scores at follow-up in a non-linear manner (e.g., wearing 12 vs. 0 h/day was associated with a 16-point reduction in PTS scores at follow-up, 95% CI -29 to -2 points). CONCLUSION: Nearly half the patients who were prescribed CG found them helpful. We observed non-linear improvement in PTS severity with the use of low-pressure CG for 8-12 h/day and ≥3 days/week, providing guidance in their prescription.

Diagnostic value of D-dimers for limb deep vein thrombosis in children: A prospective study.

The present study sought to evaluate the discriminative and predictive ability of D-dimer for pediatric limb DVT. Children aged 28 days-18 years requiring imaging to rule out limb DVT, as per the treating clinical team, were enrolled in the study. The outcome was ultrasound proven DVT. The D-dimer levels were obtained around the time of imaging. Receiver operating characteristic (ROC) curves and logistic regression models were used for data analyses. In total, 296 patients were enrolled between 2017-2020; 204 patients were diagnosed with DVT (DVT[+]). Median D-dimer levels were 2.3 µg/ml FEU (25th-75th percentile 0.9-3.9) among DVT(+) and 1.9 µg/ml FEU (25th-75th percentile 0.8-4.0) among DVT(-) patients (p = 0.60). The area under the ROC curve (AUC) was 0.52 (95% confidence interval [CI] 0.45-0.59). The odds ratio for D-dimer levels was 1.00 (95% CI 0.99-1.01), holding confounders constant. In a sub-group exploratory analysis including 23 patients with no underlying conditions or co-morbidities, the AUC curve was 0.90 (95% CI 0.76-1.00). In conclusion, in this prospective cohort study of consecutive children with suspected limb DVT, D-dimer levels had poor discriminative and predictive ability for DVT. However, D-dimer levels showed better discriminative and predictive ability for DVT in an exploratory sample of patients with no underlying conditions or co-morbidities at the time of diagnosis.

Incidence and Predictors of Mental Health Outcomes Among Survivors of Adolescent and Young Adult Cancer: A Population-Based Study Using the IMPACT Cohort.

PURPOSE: Risk and predictors of long-term mental health outcomes in survivors of adolescent and young adult (AYA) cancers are poorly characterized. Mental health is consequently neglected in long-term follow-up. METHODS: We identified all AYA in Ontario, Canada age 15-21 years when diagnosed with one of six common cancers between 1992-2012 using a population-based database, and compared them with matched controls. Linkage to provincial healthcare data allowed analysis of rates of outpatient (family physician and psychiatrist) visits for psychiatric indications and time to severe psychiatric events (emergency room visit, hospitalization, and suicide). Demographic-, disease-, and treatment-related predictors of adverse outcomes, including treatment setting (adult v pediatric), were examined. RESULTS: Among 2,208 survivors and 10,457 matched controls, 5-year survivors experienced higher rates of outpatient mental health visits than controls (671 visits per 1,000 person-years v 506; adjusted rate ratio [RR] 1.3; 95% CI, 1.1 to 1.5; P = .006). Risk of a severe psychiatric episode was also increased among survivors (adjusted hazard ratio [HR], 1.2; 95% CI, 1.1 to 1.4, P = .008). Risk of a psychotic disorder-associated severe event was doubled in survivors (HR, 2.0, 95% CI, 1.3 to 2.4; P = .007) although absolute risk remained low (15-year cumulative incidence 1.7%; 95% CI, 1.0 to 2.7). In multivariable analysis, survivors treated in adult centers experienced substantially higher outpatient visit rates compared with those treated in pediatric settings (RR 1.8; 95% CI, 1.0 to 3.1; P = .04). CONCLUSION: Survivors of AYA cancer are at substantially increased risk of adverse mental health outcomes, with those treated in adult centers at particular risk. Although absolute incidence was low, survivors were at increased risk of psychotic disorder-associated severe events. Long-term mental health surveillance is warranted, as is research into effective interventions during or after cancer treatment.

Psychiatric Disorders in Adolescent and Young Adult-Onset Cancer Survivors: A Systematic Review and Meta-Analysis.

Although a cancer diagnosis during the adolescent and young adult (AYA) years is a traumatic event, and psychiatric disorders generally manifest during the AYA period, the impact of a cancer diagnosis on long-term mental health outcomes in this population is not well characterized. We conducted a systematic review and meta-analysis to determine if survivors of AYA cancers are more likely to develop psychiatric disorders. A systematic literature search of five databases, MEDLINE, CINAHL, Web of Science, EMBASE, and PsycINFO, was conducted from their inception to November 2018. The outcome measures were psychiatric disorders as per the Diagnostic Statistical Manual criteria, or psychiatric medication use. Study eligibility, appraisal, and data abstraction were independently conducted by two reviewers. Of 7934 total studies, four met eligibility criteria for the systematic review, three of which were included in the meta-analysis. Compared to cancer-free controls, survivors were at an elevated risk of mood disorders (odds ratio [OR] 1.36; 95% CI 1.19-1.55) and anxiety disorders (OR 1.16; 95% CI 1.05-1.28), but not substance-related disorders, (OR 0.88; 95% CI 0.63-1.22). The most commonly identified risk factors were the female sex and older age at diagnosis. We found higher odds of anxiety and mood disorders in AYA-onset cancer survivors. However, few AYA-specific studies currently exist that analyze psychiatric disorders using consistent and standardized methods. Additional studies confirming these findings are warranted.