Serum and Urinary Nitrites and Nitrates and Doppler Sonography in Children With Diabetes

OBJECTIVE—The aim of the present study was to evaluate serum and urinary nitric oxide (NO) concentrations in children and adolescents with diabetes compared with age-matched healthy control subjects to find out whether Doppler ultrasonography could be used to detect changes in renal resistive indexes (RIs) in children with diabetes and to assess whether there are correlations between these parameters and NO excretion. RESEARCH DESIGN AND METHODS—We studied 42 children with type 1 diabetes and 41 matched healthy control subjects, both divided into prepubertal or pubertal children. Serum and urinary nitrite and nitrate (NO2−+NO3−) concentrations were evaluated as an index of NO production. Doppler ultrasonographic registration of intrarenal RI was performed. RESULTS—Compared with healthy control subjects, children with diabetes had significantly increased concentrations of serum (30.26 ± 6.52 vs. 24.47 ± 7.27 mmol/l, P = 0.001) and urinary NO2−+NO3− (345.07 ± 151.35 vs. 245.86 ± 80.25 mmol/l, P = 0.002); the same was true for Doppler RI values (0.64 ± 0.03 vs. 0.60 ± 0.04, P = 0.035). This occurs in both prepubertal and the pubertal children. A significant positive correlation was found between serum and urinary NO2−+NO3− levels (P = 0.002, r = 0.374). Serum NO2−+NO3− concentrations also correlated positively with Doppler RI (P = 0.032, r = 0.262) and HbA1c (A1C) (P = 0.004, r = 0.329); urinary NO2−+NO3− concentrations correlated positively with A1C (P = 0.001, r = 0.394). Doppler RI correlated positively with A1C (P = 0.000, r = 0.424). CONCLUSIONS—This study demonstrates that in children with diabetes, chronic hyperglycemia may act through a mechanism that involves increased NO production and/or action and contributes to generating intrarenal hemodynamic abnormalities, which are detectable by Doppler ultrasonography even in early diabetic nephropathy

Is a Genetic Variant associated with Bipolar Disorder Frequent in People without Bipolar Disorder but with Characteristics of Hyperactivity and Novelty Seeking?

Objective: The objective is to verify whether a genetic condition associated with bipolar disorder (BD) is frequent in old adults adapted to their environment, without BD, but with aptitudes for hyperactivity and novelty seeking (H/NS). Methods: In this cross-sectional study, the study sample included healthy elderly people (40 participants, aged 60 or older) living in an urban area and recruited from a previous study on physical exercise and active aging, who were compared with 21 old adults with BD from the same area. The genetic methodology consisted of blood sampling, DNA extraction, real-time PCR jointly with FRET probes, and the SANGER sequencing method. The genetic variant RS1006737 of CACNA1C, found to be associated with bipolar disorder diagnosis, was investigated. Results: The frequency of the RS1006737 genetic variant in the study group (H/NS) is not higher than in the BD group and is statistically significantly higher than in all the control groups found in the literature. However, the familiarity for BD is higher in old adults with BD than in the H/NS sample without BD. The risk of BD in the family (also considering those without BD but with family members with BD) is not associated with the presence of the genetic variant examined. Conclusion: The study suggests that the gene examined is associated with characteristics of hyperactivity rather than just BD. Nevertheless, choosing to participate in an exercise program is an excessively general way to identify H/NS. The next step would be to identify the old adults with welldefined H/NS features with an adequate tool

The Impact on Anxiety Symptoms of an Immersive Virtual Reality Remediation Program in Bipolar Disorders: A Randomized Clinical Trial

: Background: The objective of this work is to investigate the effectiveness of a cognitive remediation intervention on anxiety symptoms in people with bipolar disorder and the therapeutic effect on people whose anxiety symptoms were above the threshold for a screener and whose comorbidity could be identified as an anxiety disorder. Methods: The experimental intervention included 24 sessions (around 45 min each), two for each week over three months. The entire program was inspired by user-centered rehabilitation principles in a recovery-oriented perspective and an approach to bipolar disorder in an evolutionary and non-discriminating vision. The primary outcomes measure the score of the Zung Self-Rating Anxiety Scale (SAS), hypothesizing a higher decrease in the experimental group than in the control group. The survey has been conducted per the CONSORT guidelines for feasibility studies. Results: We evaluate a decrease in the overall SAS score from T0 to T1 to be higher in the experimental group compared to the control group, indicating an improvement in anxiety symptoms (p < 0.0001). Conclusions: The study suggests that virtual reality could have a role in treating anxiety symptoms and disorders in young adults with bipolar disorders or anxiety symptoms in people with hyperactivity and novelty-seeking behaviorsunder stress and high risk for bipolar disorder

Virtual Reality Cognitive Remediation in Older Adults with Bipolar Disorder: The Effects on Cognitive Performance and Depression in a Feasibility Randomized Controlled Trial

Introduction: Dementia, depression, and cardiovascular disease are major public health concerns for older adults, requiring early intervention. This study investigates whether a virtual reality cognitive remediation program (VR-CR) can improve cognitive function and depressive symptoms in older adults, and determines the necessary sample size for future studies. Integrated VR and CR interventions have shown promising outcomes in older adults with neurodegenerative and mental health disorders. Methods: This secondary analysis of a randomized controlled trial involves adults aged 58–75 years with bipolar disorder, excluding those with acute episodes, epilepsy, or severe eye diseases. The experimental group received standard treatment plus VR-CR, while the control group received only standard treatment. Results: No baseline differences were found between the experimental and control groups. No significant improvement was observed in the overall cognitive function test (p = 0.897) or in depressive symptoms (p = 0.322). A phase III efficacy study requires a sample size of 28 participants (alpha = 0.05, beta = 0.20). Conclusions: VR-CR can potentially treat depressive symptoms in adults and older adults, but the results support conducting phase III studies to further investigate these outcomes. However, the improvement in cognitive performance in the elderly is less pronounced than in younger individuals

Can Virtual Reality Cognitive Remediation in Bipolar Disorder Enhance Specific Skills in Young Adults through Mirror Neuron Activity?—A Secondary Analysis of a Randomized Controlled Trial

Introduction: Impairments in social cognition and cognitive deficits in bipolar disorder (BD) offer insights into the disorder’s progression. Understanding how interventions impact both cognitive and emotional aspects of social cognition is essential. This study examines the effects of virtual reality (VR) cognitive remediation on cognitive skills, stratified by age, in the early stages of the disorder. Methods: A secondary analysis of a randomized controlled trial (RCT) compared the efficacy of VR cognitive remediation on cognitive skills between young adults (≤58 years) and older adults (≥59 years) in the experimental group with BD. Results: The experimental group included 39 participants: 24 ≤ 58 years and 15 ≥ 59 years. Young adults showed greater improvement in the Digit Span Backward (0.37 ± 0.35 vs. 0.07 ± 0.26, F = 9.882, p = 0.020) and Digit Symbol tests (3.84 ± 3.05 vs. 1.16 ± 3.8, F = 5.895, p = 0.020). Older adults improved more in the Frontal Assessment Battery (1.00 ± 0.95 vs. 0.54 ± 0.21, F = 5.295, p = 0.027), Matrix test (0.58 ± 0.35 vs. 0.37 ± 0.26, F = 4.606, p = 0.038), and Test of Tale (0.81 ± 0.36 vs. 0.42 ± 0.38, F = 10.115, p = 0.003). Conclusions: Young adults improved more in complex cognitive tasks, while older adults showed better results in simpler tasks. The effectiveness of VR may be due to hyperstimulation of mirror neurons. Further studies are needed to confirm these findings

A Virtual Reality Cognitive Stimulation Program as an Effective Tool Against Residual/Prodromal Depressive Symptoms in Bipolar Disorders

Background: Bipolar disorder (BD) is a severe psychiatric illness characterized by a chronic course and recurrent episodes, including residual depressive symptoms even during euthymic phases. These symptoms, although not meeting criteria for a depressive episode, are linked to relapse risk and impaired social functioning. This study aims to assess whether Virtual Reality Cognitive Remediation Training reduces depressive symptoms below the clinical threshold in individuals with BD. Methods: This post hoc analysis focuses on the secondary outcome (PHQ9) of a randomized–controlled trial. Participants were recruited from the Center of Liaison Psychiatry and Psychosomatics in Italy. The experimental group received Virtual Reality Cognitive Remediation, while the control group received standard treatment Results: Data from 39 individuals in the experimental group and 25 in the control group were analyzed. A greater reduction in PHQ-9 scores (>9) was observed in the experimental group (71.8% to 48.7%) compared to the control group. Significant improvements in total PHQ-9 scores and specific symptoms were noted in the experimental group compared to the control group. Conclusions: The study highlights the significant impact of virtual reality intervention on reducing depressive symptoms in bipolar disorder. This promising outcome underscores the potential preventive role of cognitive stimulation in relapse prevention. The intervention could offer valuable benefits for both treatment and prevention strategies in bipolar disorder

Improving Social and Personal Rhythm Dysregulation in Young and Old Adults with Bipolar Disorder: Post-Hoc Analysis of a Feasibility Randomized Controlled Trial Using Virtual Reality-Based Intervention

Introduction: Rehabilitative interventions employing technology play a crucial role in bipolar disorder (BD) treatment. The study aims to appraise the virtual reality (VR)-based cognitive remediation (CR) and the interpersonal rhythm approaches to treatment outcomes of BD across different age groups. Methods: Post-hoc analysis of a 12-week randomizedcontrolled cross-over feasibility trial involving people with mood disorders (BD, DSM-IV) aged 18–75 years old: thirty-nine exposed to the experimental VR-based CR vs 25 waiting list controls. People with BD relapse, epilepsy or severe eye diseases (due to the potential VR risks exposure) were excluded. Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) was used to measure the outcome. Results: Cases and controls did not statistically significantly differ in age and sex distributions. Personal rhythm scores improved over the study follow-up in the experimental vs the control group (APC = 8.7%; F = 111.9; p < 0.0001), both in young (18–45 years) (APC = 5.5%; F = 70.46; p < 0.0001) and, to a lesser extent, older (>46 years) adults (APC = 10.5%; F = 12.110; p = 0.002). Conclusions: This study observed improved synchronization of personal and social rhythms in individuals with BD after a virtual reality cognitive remediation intervention, particularly in social activity, daily activities, and chronotype, with greater benefits in the younger population

The impact of MDQ positivity on quality of life impairment: Does it support the hypothesis of “Dysregulation of Mood, Energy, and Social Rhythms Syndrome” (DYMERS)?

Background: DSM-5 separates bipolar (BD) from depressive disorders, but some experts consider BD as part of a spectrum of mood disorders. The interpretation of numerous false positives of BD screened by the Mood Disorders Questionnaire (MDQ) is part of this debate. Recent study results suggest that the worsening of health-related quality of life (H-Qol) associated with MDQ positivity does not depend solely on mood disorders. This study aims to clarify whether the impairment may be due to other concomitant disorders, unrelated to mood disorders, leading to a worsening of H-Qol. Additionally, the study aims to explore if MDQ positivity itself observe clinical significance. // Design and methods: The study involved pairs of cases (MDQ+) and controls (MDQ−) matched for sex, age, and absence of DSM-IV psychiatric comorbidity. The impact of MDQ positivity on the quality of life in a sample of MDQ+ comorbid with MDD was measured and compared to impact of MDD in other chronic disorders. // Results: The H-Qol was significantly worse in MDQ+ than in controls (both groups without any psychiatric co-morbidity). The worsening was similar to severe chronic disorders The burden of worsening quality of life due to MDD was mild in another sample of MDQ positives with comorbid MDD. // Conclusion: The study hypothesizes that MDQ positivity may be related to hyperactivation and dysregulation of rhythms typical of stress disorders. In fact, MDQ+ was found strongly related to sleep disturbances. Future studies could verify if a “Dysregulation of Mood, Energy, and Social Rhythms Syndrome” (DYMERS), causes worsening the H-Qol in MDQ+

Cognitive Impairment and Risk of Depressive Episodes from a Bipolar Spectrum Perspective: A Case-Control Study in Older Adults during the COVID-19 Lockdown

Background: A wide range of conditions, including mixed depressive symptoms, hyperactivity, cognitive impairment (CI) might be expressions of Bipolar Spectrum Disorder (BSD) according to the neo-Kraepelinian perspective, even in advanced age. CI, which has a high prevalence in the elderly population, when it occurs in comorbidity with depression further hinders therapy response and functional ability. The present study aims to explore risk factors associated with CI in elderly individuals experiencing a depressive episode during lockdown a period marked by significant stressors and rhythm disruption. Methods: A case-control study analyzed data from a previous RCT (secondary analyses) on elderly individuals living at home, assessing depressive symptoms, cognitive performance, hyperactivity, and hypertension before (T0) and during lockdown (T1). Results: Participants with lower pre-pandemic cognitive performance were more prone to lockdown depression compared to those with higher baseline function (F = 6.074; p = 0.016). Among those experiencing lockdown depression without prior depression, those with low cognitive performance were more prevalent than the control group without depression (OR = 11.8; p = 0.015). Conclusion: This study highlights a potentially vulnerable subgroup within the elderly population that requires targeted interventions and support during stressful events. Future research should explore the underlying mechanisms linking cognitive decline and depression in older adults, particularly those with a possible bipolar spectrum predisposition

The impact of MDQ positivity on quality of life impairment: Does it support the hypothesis of Dysregulation of Mood, Energy, and Social Rhythms Syndrome (DYMERS)?

Background: DSM-5 separates bipolar (BD) from depressive disorders, but some experts consider BD as part of a spectrum of mood disorders. The interpretation of numerous false positives of BD screened by the Mood Disorders Questionnaire (MDQ) is part of this debate. Recent study results suggest that the worsening of health-related quality of life (H-Qol) associated with MDQ positivity does not depend solely on mood disorders. This study aims to clarify whether the impairment may be due to other concomitant disorders, unrelated to mood disorders, leading to a worsening of H-Qol. Additionally, the study aims to explore if MDQ positivity itself observe clinical significance.Design and methods: The study involved pairs of cases (MDQ+) and controls (MDQ-) matched for sex, age, and absence of DSM-IV psychiatric comorbidity. The impact of MDQ positivity on the quality of life in a sample of MDQ+ comorbid with MDD was measured and compared to impact of MDD in other chronic disorders.Results: The H-Qol was significantly worse in MDQ+ than in controls (both groups without any psychiatric co-morbidity). The worsening was similar to severe chronic disorders The burden of worsening quality of life due to MDD was mild in another sample of MDQ positives with comorbid MDD.Conclusion:The study hypothesizes that MDQ positivity may be related to hyperactivation and dysregulation of rhythms typical of stress disorders. In fact, MDQ+ was found strongly related to sleep disturbances. Future studies could verify if a "Dysregulation of Mood, Energy, and Social Rhythms Syndrome" (DYMERS), causes worsening the H-Qol in MDQ+