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Meta-analysis and meta-regression of diagnostic test accuracy of connectome-based predictive modeling in OCD

Tural, Umit; Gaggi, Naomi L; Stern, Emily R; Iosifescu, Dan V
Functional magnetic resonance imaging studies have reported disruptions in functional connectivity within brain networks, known as connectomes. Researchers have tested connectomes to see whether they serve as biomarkers for various psychiatric conditions. This meta-analysis aims to evaluate the diagnostic test accuracy of predictive models of connectomes derived from resting-state fMRI in diagnosing obsessive-compulsive disorder. A systematic review and meta-analysis were conducted on previous studies assessing the sensitivity, specificity, and accuracy of connectome-based diagnostic models in obsessive-compulsive disorder and healthy controls. Eight studies were identified, comprising 563 individuals with obsessive-compulsive disorder and 564 healthy controls. The results revealed robust diagnostic performance with a pooled sensitivity of 0.827 (95% CI: 0.779-0.867) and specificity of 0.794 (95% CI: 0.759-0.826). Connectome-based diagnostic models demonstrated excellent clinical utility, with an area under the curve of 87% (95% CI: 84%-90%), and significant predictive power as indicated by positive (4.15) and negative (0.21) likelihood ratios, as well as strong diagnostic odds ratio of 18.69 (95% CI: 11.84-29.49). The results highlight the potential of functional connectome-based predictive modeling as a robust tool for accurately diagnosing obsessive-compulsive disorder, with possibility of future implications for early diagnosis, monitoring treatment-related changes, involving in decision modeling, and understanding the biological mechanisms underlying obsessive-compulsive disorder.
PMID: 41999456
ISSN: 1931-7565
CID: 6031912

Dose-dependent tolerability and safety of transcranial photobiomodulation: a randomized controlled trial

Coelho, David R A; Fernando Vieira, Willians; Hurtado Puerto, Aura Maria; B Gersten, Maia; Anne Collins, Katherine; Peterson, Anna; Siu, Kari; Tural, Ümit; Vlad Iosifescu, Dan; Cassano, Paolo
Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light has emerged as a promising therapy for major depressive disorder (MDD). However, the dose-dependent tolerability of t-PBM has not been adequately explored. This secondary analysis of a sham-controlled clinical trial evaluated the safety and tolerability of t-PBM across varying doses in 31 subjects with MDD. Participants were randomly assigned to receive four sessions of NIR (808 nm) t-PBM (sham, low, medium, and high doses) approximately one week apart. The outcome was the emergence of side effects, assessed by the Systematic Assessment for Treatment-Emergent Effects-Specific Inquiry (SAFTEE-SI) scale. The frequency of side effects, compared to baseline or the prior week, was analyzed using Cochran's Q test. Additionally, body weight and systolic and diastolic blood pressures (SBP and DBP, respectively) were recorded and assessed with repeated measures ANOVA. The results showed no statistically significant changes in rates of any adverse events compared to baseline or prior week. The most notable rate increases were in "delayed or absent orgasm" for the medium dose compared to baseline among 10% of participants (Cochran's Q = 6.231; p = 0.101), and in "ringing in ears or trouble hearing" for the high dose compared to the prior week among 13% of participants (Cochran's Q = 6.231; p = 0.101). There were no significant changes in weight or SBP and DBP (F(4, 85) = 0.277, p = 0.892; F(4, 87.45) = 1.722, p = 0.152; F(4, 87.10) = 1.672, p = 0.164, respectively). In conclusion, this study did not find a significant association between the dose of t-PBM sessions and rates of adverse events or changes in vital signs. The side-effect profile of t-PBM appears benign, regardless of dosimetry.
PMID: 40437278
ISSN: 1435-604x
CID: 5854672

Neurometabolite Changes After Transcranial Photobiomodulation in Major Depressive Disorder: A Randomized Controlled Trial Investigating Dose-Dependent Effects

Coelho, David R A; Tural, Ümit; Hurtado Puerto, Aura Maria; Collins, Katherine Anne; Gersten, Maia Beth; Parincu, Zamfira; Siu, Kari; Iosifescu, Dan Vlad; Ratai, Eva-Maria; Cassano, Paolo; Weerasekera, Akila
PMCID:12112509
PMID: 40429396
ISSN: 2077-0383
CID: 5855262

Noninvasive Brain Stimulation for Neurodevelopmental Disorders: A Systematic Review

López-Rodríguez, Sergi; Coelho, David R A; Renet, Christian; Vieira, Willians Fernando; Tural, Ümit; Cassano, Paolo; Camprodon, Joan A
Neurodevelopmental disorders (NDDs) affect brain development, leading to diverse cognitive, social, behavioral, and affective impairments. Noninvasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and transcranial photobiomodulation (tPBM), have been investigated as potential treatments for NDDs. The authors of this systematic review evaluated the literature on NIBS in NDDs, including double-blind, sham-controlled, randomized controlled trials. Following PRISMA guidelines and a registered protocol, the authors conducted a comprehensive search in PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycInfo, and Scopus, identifying 23 studies. TMS showed promise for addressing hyperactivity, inattention, and working memory deficits in attention-deficit hyperactivity disorder (ADHD), with outcomes influenced by coil type (H5 vs. H6) and stimulation site (right vs. left dorsolateral prefrontal cortex). tDCS showed potential for improving inattention and executive function in ADHD, with limited effects observed on reducing symptom severity in autism spectrum disorder (ASD) and dyslexia. tPBM offered specific therapeutic benefits in reducing irritability in ASD. Although NIBS generally showed mild, transient adverse effects, isolated seizure events, such as one during TMS in ADHD, highlight the importance of rigorous safety protocols, especially in NDDs with elevated epilepsy risk. This review identified potential benefits of certain NIBS protocols in NDDs; however, high variability in methodologies, sample size limitations, and bias concerns underscore the need for further research to clarify the therapeutic efficacy and safety of NIBS among patients with NDDs.
PMID: 40350963
ISSN: 1545-7222
CID: 5913392

Understanding High-Functioning Depression in Adults

Joseph, Judith F; Tural, Umit; Joseph, Nikeisha D; Mendoza, Teresa E; Patel, Eshna; Reifer, Rachel; Deregnaucourt, Margot
INTRODUCTION/BACKGROUND: High-functioning depression (HFD) is described as experiencing depressive symptoms such as fatigue, anhedonia, poor concentration, guilt, restlessness, sleep disturbances, and appetite changes without experiencing a lack of functioning or significant distress. The purpose of this study is to characterize the clinical correlates of HFD. METHODS:This study entailed a descriptive, cross-sectional design based on interviews administered to120 English-speaking participants with HFD (aged 18-75). The interview involved administering a semi-structured HFD Analysis Questionnaire, the Joseph HFD Inventory, the HFD Trauma Inventory, and the Joseph HFD Anhedonia Scale in a single, 30-minute session for each participant. Big traumas, defined as extremely traumatic events, were analyzed by the trauma inventory. RESULTS:Out of the 120 participants, 72 (60%) demonstrated HFD, and 17 (14%) demonstrated very HFD. A correlation was observed between symptoms of HFD, such as anhedonia and marital status, as post hoc tests showed that the average Anhedonia Scale score was higher for married or partnered participants than those who were single (p=0.038). As anticipated, the participants with higher Anhedonia Scale scores had higher HFD scores (p=0.003). These participants also experienced higher trauma inventory scores and big traumas. Furthermore, as participant education level increased, the number of big traumas reported decreased (p<0.001). Participants who were parents/caregivers of children also had the highest Anhedonia Scale and HFD scores (p=0.0126 and p=0.0210, respectively). CONCLUSION/CONCLUSIONS:The results supported the hypothesis that individuals with HFD have increased levels of anhedonia and trauma. However, trauma scores were inversely associated with education level in HFD.
PMCID:11831407
PMID: 39963293
ISSN: 2168-8184
CID: 5853922

Enhancing sleep, wakefulness, and cognition with transcranial photobiomodulation: a systematic review

Gaggi, Naomi L; Parincu, Zamfira; Peterson, Anna; O'Brien, Courtney; Kam, Korey; Tural, Umit; Ayappa, Indu; Varga, Andrew W; Iosifescu, Dan V; Osorio, Ricardo S
Disruptions in sleep are common across clinical populations, particularly those with neurological and psychiatric disorders, making restorative sleep and sustained wakefulness a public health priority. Sleep is essential for brain function, impacting cognition in addition to serving as a critical factor in memory consolidation and healthy aging. Neuromodulation via transcranial photobiomodulation (t-PBM) increases cerebral mitochondrial activity and blood flow. These effects may underlie improvements in sleep quality and wakefulness observed after t-PBM. In this systematic review, we summarize the current literature across clinical and healthy populations, which describes t-PBM's potential to improve sleep, wakefulness, and cognition. The scope of this review also includes t-PBM's effect on the brain's glymphatic system and blood flow, the potential of this strategy to augment alertness, wakefulness, and associated cognitive processes, and the suggestion for targeted t-PBM application for future research based on the underlying neurobiological mechanisms of t-PBM and wakefulness across diverse clinical populations.
PMCID:12350269
PMID: 40822571
ISSN: 1662-5153
CID: 5908762

Personality characteristics, not clinical symptoms, are associated with anhedonia in a community sample: A preliminary investigation

Tobe, Russell H; Tu, Lucia; Keefe, John R; Breland, Melissa M; Ely, Benjamin A; Sital, Melissa; Richard, Jasmin T; Tural, Umit; Iosifescu, Dan V; Gabbay, Vilma
Anhedonia is a salient transdiagnostic psychiatric symptom associated with increased illness severity and chronicity. Anhedonia is also present to varying degrees in non-clinical cohorts. Here, we sought to examine factors influencing expression of anhedonia. Participants (N = 335) were recruited through the Nathan Kline Institute-Rockland Sample, an initiative to deeply phenotype a large community sample across the lifespan. Utilizing a data-driven approach, we evaluated associations between anhedonia severity, indexed by Snaith-Hamilton Pleasure Scale (SHAPS), and 20 physical, developmental, and clinical measures, including Structured Clinical Interview for DSM-IV, Beck Depression Inventory, State-Trait Anxiety Inventory, NEO Five-Factor Inventory-3 (NEO-FFI-3), BMI, Hemoglobin A1C, and demography. Using a bootstrapped AIC-based backward selection algorithm, seven variables were retained in the final model: NEO-FFI-3 agreeableness, extraversion, and openness to experience; BMI; sex; ethnicity; and race. Though median SHAPS scores were greater in participants with psychiatric diagnoses (18.5) than those without (17.0) (U = 12238.5, z = 2.473, p = 0.013), diagnosis and symptom measures were not retained as significant predictors in the final robust linear model. Participants scoring higher on agreeableness, extraversion, and openness to experience reported significantly lower anhedonia. These results demonstrate personality as a mild-to-moderate but significant driver of differences in experiencing pleasure in a community sample.
PMID: 37922596
ISSN: 1879-1379
CID: 5611652

Efficacy of Transcranial Photobiomodulation on Depressive Symptoms: A Meta-Analysis

Cho, Yoonju; Tural, Umit; Iosifescu, Dan V
PMCID:10518694
PMID: 37651208
ISSN: 2578-5478
CID: 5618172

Comparison of Adiponectin Levels in Anorexia Nervosa, Bulimia Nervosa, Binge-Eating Disorder, Obesity, Constitutional Thinness, and Healthy Controls: A Network Meta-Analysis

Tural, Umit; Sparpana, Allison; Sullivan, Elizabeth; Iosifescu, Dan V
Adiponectin is a protein hormone that is produced and secreted primarily by adipose tissue. The levels of adiponectin in those with eating disorders, obesity, and healthy controls have been extensively studied. However, the general picture of the differences in adiponectin levels across the mentioned conditions is still unclear and fragmented. In this study, we pooled previous studies and performed a network meta-analysis to gain a global picture of comparisons of adiponectin levels across eating disorders, obesity, constitutional thinness, and healthy controls. Electronic databases were searched for anorexia nervosa, avoidant restrictive food intake disorder, binge-eating disorder, bulimia nervosa, healthy controls, night eating syndrome, obesity, and constitutional thinness in studies where adiponectin levels were measured. A total of 4262 participants from 50 published studies were included in the network meta-analysis. Adiponectin levels were significantly higher in participants with anorexia nervosa than in healthy controls (Hedges' g = 0.701, p < 0.001). However, adiponectin levels in constitutionally thin participants were not significantly different from those of healthy controls (Hedges' g = 0.470, p = 0.187). Obesity and binge-eating disorder were associated with significantly lower adiponectin levels compared to those of healthy controls (Hedges' g = -0.852, p < 0.001 and Hedges' g = -0.756, p = 0.024, respectively). The disorders characterized by excessive increases or decreases in BMI were associated with significant changes in adiponectin levels. These results suggest that adiponectin may be an important marker of severely disequilibrated homeostasis, especially in fat, glucose, and bone metabolisms. Nonetheless, an increase in adiponectin may not simply be associated with a decrease in BMI, as constitutional thinness is not associated with a significant increase in adiponectin.
PMCID:10220738
PMID: 37240826
ISSN: 2075-1729
CID: 5544012

Suicidal ideation and behavior in schizophrenia: The role of negative urgency and psychiatric symptoms [Letter]

Hoptman, Matthew J; Tural, Umit; Arnold, Molly S; Collins, Katherine A; Evans, Kathryn T; Irvin, Molly K; Parincu, Zamfira; Rette, Danielle N; Sparpana, Allison M; Sullivan, Elizabeth F; Iosifescu, Dan V
PMID: 36906943
ISSN: 1573-2509
CID: 5448772